Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity.
Abstract
Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family of structurally related proteins that promote neuronal differentiation and survival during development, is a potent modulator of synaptic plasticity. Changes in BDNF expression, release and neuromodulatory activity, mediated by both epigenetic and post-translational mechanisms, have been associated with many pathological conditions and developmental experiences, such as maternal deprivation and environmental enrichment. Much effort has been devoted to studying plasticity in the hippocampus, a structure traditionally associated with learning and memory, yet there is increasing empirical support for the contribution of another structure--the amygdala--to BDNF-induced changes. Because the amygdala is a critical site for emotional memory formation, and many emotional and neurodevelopmental pathologies have been linked to amygdala-based abnormalities, considerable efforts have been devoted to the characterization of its circuitry. Here we review the role of BDNF as a biochemical integrator of convergent cellular signals, and as a central driver of neural plasticity. We conclude by emphasizing the importance of characterizing BDNF signaling cascades in behaviorally-relevant networks, to identify potential drug targets for novel therapeutic interventions.
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Brain-derived neurotrophic factor is a centrally produced neurotrophin of particular interest due to its high concentration within the hippocampus and its integral role in supporting neuronal survival and growth, and synaptic plasticity.
“Brain-derived neurotrophic factor (BDNF) is a centrally produced neurotrophin of particular interest due to its high concentration within the hippocampus and its integral role in supporting neuronal survival and growth, and synaptic plasticity (Cotman et al., 2007; Cowansage et al., 2010).”
From Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment (2016) · cites this paper as Cowansage et al., 2010
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Autry, A. E., & Monteggia, L. M. (2012) · Pharmacological Reviews · doi:10.1124/pr.111.005108 · Cited by 1,390 · see citing works
“Recent work has suggested that pro-BDNF (35 kDa) is secreted in an activitydependent manner along with the enzyme tissue plasminogen activator, which cleaves pro-BDNF to mature BDNF (14 kDa) (Waterhouse and Xu, 2009).”
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Johansen, J. P., Cain, C. K., Ostroff, L. E., & LeDoux, J. E. (2011) · Cell · doi:10.1016/j.cell.2011.10.009 · Cited by 1,012 · see citing works
“Neurotrophin Signaling Neurotrophin signaling has also been implicated in fear memory consolidation (Cowansage et al., 2010; Rattiner et al., 2005).”
Self-citationBridging animal and human models of exercise-induced brain plasticity
Voss, M. W., Vivar, C., Kramer, A. F., & van Praag, H. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.08.001 · Cited by 1,030 · see citing works
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Leal, G., Comprido, D., & Duarte, C. B. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.005 · Cited by 685 · see citing works
“The neurotrophin brain-derived neurotrophic factor (BDNF) has been shown to play a key role asmediator of activity-induced LTP in the hippocampus as well as in other brain regions (Bramham and Messaoudi, 2005; Cowansage et al., 2010; Lu et al., 2008; Minichiello, 2009; Park and Poo, 2013; Santos et al., 2010).”
Histone acetylation: molecular mnemonics on the chromatin
Gräff, J., & Tsai, L.-H. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3427 · Cited by 680 · see citing works
Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis
Stilling, R. M., Dinan, T. G., & Cryan, J. F. (2014) · Genes, Brain and Behavior · doi:10.1111/gbb.12109 · Cited by 637 · see citing works
“a number of psychiatric and neurodegenerative diseases (Cowansage et al. 2010; Tapia-Arancibia et al. 2008; Walker et al. 2012).”
BackgroundPhillips, C. (2017) · Neural Plasticity · doi:10.1155/2017/7260130 · Cited by 456 · see citing works
“Neurotrophins are a closely related family of proteins in the brain that contributes to the survival, growth, and maintenance of neurons [28] and participate in a variety of learning and memory functions [29].”
BackgroundThe role of CREB and BDNF in neurobiology and treatment of Alzheimer's disease
Amidfar, M., de Oliveira, J., Kucharska, E., Budni, J., & Kim, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118020 · Cited by 413 · see citing works
The involvement of BDNF, NGF and GDNF in aging and Alzheimer's disease
Josiane, Tatiani, Francielle, Michelle, M., & Alexandra (2015) · Aging and Disease · doi:10.14336/ad.2015.0825 · Cited by 409 · see citing works
“[20] Cowansage KK, LeDoux JE, Monfils MH (2010).”
BackgroundOomen, C. A., Soeters, H., Audureau, N., Vermunt, L., van Hasselt, F. N., Manders, E. M. M., Joëls, M., Lucassen, P. J., & Krugers, H. J. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0247-10.2010 · Cited by 352 · see citing works
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BackgroundMaaß, A., Düzel, S., Brigadski, T., Goerke, M., Becke, A., Sobieray, U., Neumann, K., Lövdén, M., Lindenberger, U., Bäckman, L., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.10.084 · Cited by 358 · see citing works
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BackgroundYang, J., Harte‐Hargrove, L. C., Siao, C.-J., Marinic, T. E., Clarke, R., Ma, Q., Jing, D., LaFrancois, J. J., Bath, K. G., Mark, W. H., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.040 · Cited by 333 · see citing works
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BackgroundPhillips, C. (2017) · Neural Plasticity · doi:10.1155/2017/3589271 · Cited by 335 · see citing works
“in brain-derived neurotrophic factor (BDNF) [18].”
Mansur, R. B., Brietzke, E. M., & McIntyre, R. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.12.017 · Cited by 325 · see citing works
Luo, H., Xiang, Y., Qu, X., Liu, H., Liu, C., Li, G., Han, L., & Qin, X. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00395 · Cited by 268 · see citing works
Curley, J. P., & Champagne, F. A. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.11.001 · Cited by 257 · see citing works
“It is also clear, that there are sensitive periods for the impact of maternal care that are shaped by neurobiological and behavioral changes that accompany the transition to independence (Pena et al., 2013; Upton and Sullivan, 2010; Hess, 1959; Curley et al., 2009; Franks et al., 2015).”
BackgroundInfluentialJeanneteau, F. D., Lambert, W. M., Ismaili, N., Bath, K. G., Lee, F. S., Garabedian, M. J., & Chao, M. V. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114122109 · Cited by 252 · see citing works
“BDNF and its receptor, TrkB, are both expressed in the PVN (8, 9) and many other brain regions, and display dramatic effects upon neuroprotection and synaptic plasticity (10, 11).”
BackgroundMartínez‐Ballesta, M. D. C., Gil‐Izquierdo, Á., García‐Viguera, C., & Domínguez‐Perles, R. (2018) · Foods · doi:10.3390/foods7050072 · Cited by 262 · see citing works
Caccamo, A., Maldonado, M. A., Bokov, A. F., Majumder, S., & Oddo, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012851108 · Cited by 249 · see citing works
“One of these proteins is brain-derived neurotrophic factor (BDNF), which is known to facilitate synaptic plasticity and memory formation (26) and has been proposed to play a role in the pathogenesis of AD, with reduced BDNF levels detected in AD brains (27, 28).”
BackgroundBrain-Derived Neurotrophic Factor: Three Ligands, Many Actions.
Hempstead, B. L. (2015) · Europe PMC (PubMed Central) · Cited by 203 · see citing works
Microbiota-gut-brain axis and cognitive function
Gareau, M. G. (2014) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4939-0897-4_16 · Cited by 189 · see citing works
Oertel-Knöchel, V., Mehler, P., Thiel, C., Steinbrecher, K., Malchow, B., Tesky, V., Ademmer, K., Prvulovic, D., Banzer, W., Zopf, Y., et al. (2014) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-014-0485-9 · Cited by 185 · see citing works
“BDNF is of special interest regarding its role in synaptic plasticity and growth [15, 42].”
BackgroundRothman, S. M., Griffioen, K. J., Wan, R., & Mattson, M. P. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06525.x · Cited by 185 · see citing works
Hippocampal–Prefrontal BDNF and Memory for Fear Extinction
Rosas-Vidal, L. E., Do-Monte, F. H., Sotres-Bayon, F., & Quirk, G. J. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.64 · Cited by 184 · see citing works
“There is growing interest in the mechanisms of BDNF effects on plasticity underlying fear extinction learning (Andero and Ressler, 2012; Cowansage et al, 2010).”
BackgroundRosenblat, J. D., Brietzke, E., Mansur, R. B., Maruschak, N. A., Lee, Y., & McIntyre, R. S. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.08.058 · Cited by 172 · see citing works
“Of note, BDNF levels as a predictor of cognitive function in BD has been of particular interest and is extensively reviewed elsewhere (Cowansage et al., 2010; Bauer et al., 2014).”
BackgroundKundaković, M., Lim, S. C., Gudsnuk, K. M., & Champagne, F. A. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00078 · Cited by 172 · see citing works
Bitner, R. S. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.11.009 · Cited by 163 · see citing works
Brain-Derived Neurotrophic Factor, Food Intake Regulation, and Obesity
Rosas‐Vargas, H., Martínez‐Ezquerro, J. D., & Bienvenu, T. (2011) · Archives of Medical Research · doi:10.1016/j.arcmed.2011.09.005 · Cited by 160 · see citing works
“In contrast, mature BDNF preferentially binds to the TrkB receptor, promoting development and differentiation of neurons (33,34), cell survival (35e37), long-term potentiation (38,39), and synaptic plasticity (40,41) achieved by a combination of three signaling cascades: the mitogen-activated protein kinase (MAPK) (42…”
BackgroundTsai, C., Ukropec, J., Ukropcová, B., & Pai, M. (2017) · NeuroImage Clinical · doi:10.1016/j.nicl.2017.10.028 · Cited by 156 · see citing works
“BDNF, a member of the neurotrophin family of factors, supports neural growth and survival and synaptic plasticity, and is highly concentrated in the hippocampus and cortex (Cowansage et al., 2010; Gottmann et al., 2009; Lipsky and Marini, 2007).”
Kandola, A., Hendrikse, J., Lucassen, P. J., & Yücel, M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00373 · Cited by 155 · see citing works
“Brain-derived neurotrophic factor (BDNF) is a centrally produced neurotrophin of particular interest due to its high concentration within the hippocampus and its integral role in supporting neuronal survival and growth, and synaptic plasticity (Cotman et al., 2007; Cowansage et al., 2010).”
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“Brain-derived neurotrophic factor (BDNF), which impacts cellular survival and differentiation during CNS development (Cohen-Cory et al., 2010), plays a crucial role during brain recovery after stroke (Berretta et al., 2014; Cowansage et al., 2010).”
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Béjot, Y., Prigent‐Tessier, A., Cachia, C., Giroud, M., Mossiat, C. M., Bertrand, N., Garnier, P. E., & Marie, C. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.10.019 · Cited by 151 · see citing works
“BDNF also represents a crucial signalling molecule in adaptative brain plasticity after stroke (Cowansage et al., 2010 ; Lipsky and Marini, 2007; Mattson, 2008).”
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Zagrebelsky, M., Tacke, C., & Korte, M. (2020) · Cell and Tissue Research · doi:10.1007/s00441-020-03226-5 · Cited by 147 · see citing works
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Logrip, M. L., Barak, S., Warnault, V., & Dorit Ron, A. (2015) · Brain Research · doi:10.1016/j.brainres.2015.03.025 · Cited by 145 · see citing works
“BDNF regulates a variety of neuronal processes, including neuronal development, neuroprotection, synaptic plasticity and learning and memory (Castren, 2004; Cowansage et al., 2010; Lu et al., 2014; Lu et al., 2008; Minichiello, 2009).”
BackgroundSo, N., Franks, B., Lim, S., & Curley, J. P. (2015) · PLOS ONE · doi:10.1371/journal.pone.0134509 · Cited by 135 · see citing works
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BackgroundBrain-derived neurotrophic factor
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Garofalo, S., D’Alessandro, G., Chece, G., Brau, F., Maggi, L., Rosa, A., Porzia, A., Mainiero, F., Esposito, V., Lauro, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms7623 · Cited by 129 · see citing works
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Rana, T., Behl, T., Sehgal, A., Srivastava, P., & BUNGAU, S. G. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01754-x · Cited by 127 · see citing works
Géral, C., Angelova, A., & Lesieur, S. (2013) · Pharmaceutics · doi:10.3390/pharmaceutics5010127 · Cited by 124 · see citing works
“neurotrophin-based drug delivery system should be evaluated by its capacity to modulate the BDNF levels and activate receptor TrkB signaling [35–87].”
BackgroundRegulation of local translation at the synapse by BDNF
Santos, A. R., Comprido, D., & Duarte, C. B. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.08.004 · Cited by 122 · see citing works
“The role of BDNF in synaptic plasticity, as well as in acquisition, consolidation, and retention of hippocampal-dependent memory has been reviewed elsewhere (Bramham and Messaoudi, 2005; Cowansage et al., 2010; Lu et al., 2008; Minichiello, 2009) and is beyond the scope of this article.”
Eyileten, C., Kapłon‐Cieślicka, A., Mirowska-Guzel, D. M., Małek, Ł. A., & Postula, M. A. (2017) · Journal of Diabetes Research · doi:10.1155/2017/2823671 · Cited by 123 · see citing works
Fletcher, J. L., Murray, S. S., & Xiao, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19124131 · Cited by 122 · see citing works
“The expression of BDNF itself is regulated by neural activity [62,63] (Figure 1a), including sensory and environmental experiences [64,65].”
BackgroundKhalin, I., Alyautdin, R. N., Wong, T. W., Gnanou, J. V., Kocherga, G., & Kreuter, J. (2016) · Drug Delivery · doi:10.1080/10717544.2016.1199609 · Cited by 117 · see citing works
“Our data are supported by numerous reviews devoted to neuroprotective properties of BDNF (Cowansage et al., 2010; Géral et al., 2013; Khalin et al., 2015) and consistent with many experimental studies.”
ResultHortopan, G. A., Dinday, M. T., & Baraban, S. C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1887-10.2010 · Cited by 111 · see citing works
“One of these previously described genes, BDNF, a member of the “neurotrophin” family of growth factors, is believed to play a role in synaptic plasticity and excitability (Croll et al., 1999; Cowansage et al., 2010).”
BackgroundHippocampal BDNF in physiological conditions and social isolation
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“BDNF uses a dual receptor system – it preferentially binds to the TrkB receptor (Cowansage et al., 2010) but also binds to a low-affinity receptor, p75 neurotrophin receptor (p75 NTR) (Chao, 2003) (Figure 1).”
BackgroundRahn, E. J., Karlsson, M. G., & Sweatt, J. D. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.06.008 · Cited by 108 · see citing works
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Angelova, A., Angelov, B., Drechsler, M., & Lesieur, S. (2013) · Drug Discovery Today · doi:10.1016/j.drudis.2013.07.010 · Cited by 105 · see citing works
Llorente, R., Miguel-Blanco, C., Aisa, B., Lachize, S., Borcel, É., Meijer, O. C., Ramírez, M. J., de Kloet, E. R., & Viveros, M. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02109.x · Cited by 101 · see citing works
Harte‐Hargrove, L. C., MacLusky, N. J., & Scharfman, H. E. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.12.029 · Cited by 100 · see citing works
Emerging Roles of the Mitogen and Stress Activated Kinases MSK1 and MSK2
Reyskens, K. M. S. E., & Arthur, J. S. C. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00056 · Cited by 100 · see citing works
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BackgroundQi, D., Ouyang, C., Wang, Y., Zhang, S., Ma, X., Song, Y., Yu, H., Tang, J., Fu, W. E., Sheng, L., et al. (2014) · Brain Research · doi:10.1016/j.brainres.2014.06.031 · Cited by 94 · see citing works
Serafini, G., Pompili, M., Hansen, K. F., Obrietan, K. H., Dwivedi, Y., Shomron, N., & Girardi, P. (2013) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-013-9997-5 · Cited by 93 · see citing works
“BDNF has been suggested to promote neuronal differentiation and cell survival during development (Cowansage et al. 2010).”
BackgroundNin, M. S. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00073 · Cited by 86 · see citing works
“The synthesis and release of BDNF by these pyramidal neurons provides evidence for both a paracrine and an autocrine role for BDNF and establishes a local source of trophic support for the maintenance of synaptic plasticity in the mature brain (Wetmore et al., 1994; Waterhouse and Xu, 2009; Cowansage et al., 2010).”
BackgroundThe tripartite glutamatergic synapse
Lalo, U., Koh, W., Lee, C. J., & Pankratov, Y. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108758 · Cited by 86 · see citing works
The Role of BDNF in the Development of Fear Learning
Dincheva, I., Lynch, N. B., & Lee, F. S. (2016) · Depression and Anxiety · doi:10.1002/da.22497 · Cited by 85 · see citing works
“In addition, proBDNF negatively regulates neuronal mechanisms implicated in learning and memory,[17, 19, 23, 24] again indicating an opposite role in synaptic plasticity compared to mature BDNF.”
BackgroundGawali, N. B., Bulani, V. D., Gursahani, M., Deshpande, P. S., Kothavade, P. S., & Juvekar, A. R. (2017) · Brain Research · doi:10.1016/j.brainres.2017.03.004 · Cited by 88 · see citing works
Involvement of Brain-Derived Neurotrophic Factor in Late-Life Depression
Dwivedi, Y. (2013) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2012.10.026 · Cited by 86 · see citing works
COMT Val158Met Genotype and Individual Differences in Executive Function in Healthy Adults
Wishart, H. A., Roth, R. M., Saykin, A. J., Rhodes, C. H., Tsongalis, G. J., Pattin, K. A., Moore, J. H., & McAllister, T. W. (2010) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617710001402 · Cited by 84 · see citing works
G-Protein Coupled Receptors and Tau-different Roles in Alzheimer’s Disease
Chidambaram, H., & Chinnathambi, S. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.04.019 · Cited by 87 · see citing works
Broderick, T. L., Rasool, S., Li, R., Zhang, Y., Anderson, M., Al‐Nakkash, L., Plochocki, J. H., Geetha, T., & Babu, J. R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197337 · Cited by 86 · see citing works
“In pregnant rats, Resv differentially activates promoters of the BDNF gene [31] and increases the expression of BDNF in the primary culture of neurons and glial cells [32], suggesting a potential role in synaptic plasticity and memory formation [33].”
BackgroundMelatonin and neurotrophins NT-3, BDNF, NGF in patients with varying levels of depression severity
Ogłodek, E. A., Just, M. J., Szromek, A. R., & Araszkiewicz, A. S. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.04.003 · Cited by 83 · see citing works
“trophins regulate a wide variety of neural functions, acting upon 5NTR, TrkA, TrkB and TrkC receptors [15,16].”
BackgroundFischer, A. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.11.039 · Cited by 82 · see citing works
“A number of studies have demonstrated that BNDF expression and BDNF transport in various brain regions are increased in response to EE training (Bekinschtein et al., 2011) (Novkovic et al., 2015).”
BackgroundFabbri, C., Hosák, L., Mößner, R., Giegling, I., Mandelli, L., Bellivier, F., Claes, S. J., Collier, D. A., Corrales, A., DeLisi, L. E., et al. (2016) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2016.1208843 · Cited by 81 · see citing works
“BNDF is implicated in processes that modulate learning, memory and mood (Soule et al. 2006; Cowansage et al. 2010).”
BackgroundKarim, Y., Siddique, A. E., Hossen, F., Rahman, M., Mondal, V., Banna, H. U., Hasibuzzaman, M. M., Hosen, Z., Islam, M. S., Sarker, M. K., et al. (2019) · Environment International · doi:10.1016/j.envint.2019.105029 · Cited by 79 · see citing works
Brain plasticity and cognitive neurorehabilitation
Berlucchi, G. (2011) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2011.573255 · Cited by 79 · see citing works
The role of microRNAs in synaptic plasticity, major affective disorders and suicidal behavior
Serafini, G., Pompili, M., Innamorati, M., Giordano, G., Montebovi, F., Sher, L., Dwivedi, Y., & Girardi, P. (2012) · Neuroscience Research · doi:10.1016/j.neures.2012.04.001 · Cited by 80 · see citing works
Dionisie, V., Ciobanu, A. M., Toma, V. A., Manea, M. C., Baldea, I., Olteanu, D., Sevastre-Berghian, A., Clichici, S., Manea, M., Riga, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147483 · Cited by 78 · see citing works
Reichmann, F., Hassan, A. M., Farzi, A., Jain, P., Schuligoi, R., & Holzer, P. D. (2015) · Scientific Reports · doi:10.1038/srep09970 · Cited by 76 · see citing works
Yan, L., Xu, X., He, Z., Wang, S., Zhao, L., Qiu, J., Wang, D., Gong, Z., Qiu, X., & Huang, H. (2020) · BioMed Research International · doi:10.1155/2020/2794263 · Cited by 77 · see citing works
Postsynaptic BDNF signalling regulates long‐term potentiation at thalamo‐amygdala afferents
Meis, S., Endres, T., & Leßmann, V. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.220434 · Cited by 76 · see citing works
“In addition, it plays a key role as a modulator of synaptic strength (Gottmann et al. 2009; Minichiello 2009; Cowansage et al. 2010).”
BackgroundMSK1 Regulates Homeostatic and Experience-Dependent Synaptic Plasticity
Corrêa, S. A. L., Hunter, C. J., Palygin, O., Wauters, S. C., Martin, K. J., McKenzie, C., McKelvey, K., Morris, R., Pankratov, Y., Arthur, J. S. C., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0930-12.2012 · Cited by 75 · see citing works
“…BDNF mRNA and protein have been observed in rodents in response to environmental enrichment (Nithianantharajah and Hannan, 2006; Baroncelli et al., 2010), which, via the BDNF TrkB receptor, promotes dendritic growth and increased spine density in an ERK1/2-dependent manner (Cowansage et al., 2010).”
BackgroundInfluentialOxidative Imbalance and Anxiety Disorders
Krolow, R., Arcego, D. M., Noschang, C. G., Weis, S. N., & Dalmaz, C. (2014) · Current Neuropharmacology · doi:10.2174/1570159x11666131120223530 · Cited by 74 · see citing works
“Such factors regulate neuronal survival and proliferation, or promote the expansion of dendritic spines [160-162].”
Epigenetics and psychoneuroimmunology: Mechanisms and models
Mathews, H. L., & Janusek, L. W. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.08.009 · Cited by 76 · see citing works
“Brain derived neurotrophic factor (BDNF) is a growth factor that mediates neural plasticity through promotion of new synaptic connections between neurons (Greenberg et al., 2009; Cohen-Cory et al., 2010; Cowansage et al., 2010).”
BackgroundJeanblanc, J., Logrip, M. L., Janak, P. H., & Dorit Ron, A. (2012) · European Journal of Neuroscience · doi:10.1111/ejn.12067 · Cited by 72 · see citing works
“Activation of these main pathways leads to intracellular events that underlie the functions of BDNF in the central nervous system (CNS; Reichardt, 2006; Minichiello, 2009; Cowansage et al., 2010).”
BackgroundWu, W.-F., Chen, C., Lin, J.-T., Jiao, X., Dong, W., Wan, J., Liu, Q., Qiu, Y., Sun, A., Liu, Y., et al. (2024) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-024-00595-5 · Cited by 76 · see citing works
“BDNF has been identified as a crucial molecule in promoting LTP in various brain regions, including the hippocampus [62–64].”
BackgroundChronic BDNF deficiency leads to an age-dependent impairment in spatial learning
Petzold, A., Psotta, L., Brigadski, T., Endres, T., & Leßmann, V. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.02.009 · Cited by 71 · see citing works
Ginsberg, S. D., Malek-Ahmadi, M., Alldred, M. J., Chen, Y.-H., Chen, K.-W., Chao, M., Counts, S., & Mufson, E. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104540 · Cited by 68 · see citing works
Zeng, Y., Liu, Y.-K., Wu, M., Liu, J., & Hu, Q. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120886 · Cited by 70 · see citing works
Role of the central nervous system and adipose tissue BDNF/TrkB axes in metabolic regulation
Nakagomi, A., Okada, S., Yokoyama, M., Yoshida, Y., Shimizu, I., Miki, T., Kobayashi, Y., & Minamino, T. (2015) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.9 · Cited by 66 · see citing works
Zhai, X., Wu, N., Koriyama, S., Wang, C., Shi, M., Huang, T., Wang, K., Sawada, S. S., & Xiang, F. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18010289 · Cited by 69 · see citing works
“This link may be attributed to the BDNF, which is a neurotrophin having roles in the maintenance of neurons involved in emotional and cognitive function [69].”
BackgroundGinsberg, S. D., Malek‐Ahmadi, M. H., Alldred, M. J., Che, S., Elarova, I., Chen, Y., Jeanneteau, F. D., Kranz, T. M., Chao, M. V., Counts, S., et al. (2017) · Hippocampus · doi:10.1002/hipo.22802 · Cited by 69 · see citing works
Impaired fear extinction learning in adult heterozygous BDNF knock-out mice
Psotta, L., Leßmann, V., & Endres, T. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.03.003 · Cited by 68 · see citing works
Hriţcu, L., & Gorgan, L. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.01.016 · Cited by 70 · see citing works
“Also, BDNF plays a critical role in synaptic plasticity and memory processes (Cowansage et al., 2010; Musumeci and Minichiello, 2011; Yu et al., 2009).”
BackgroundPhillips, C. (2017) · Neural Plasticity · doi:10.1155/2017/7014146 · Cited by 65 · see citing works
“Neurotrophins—vital proteins in the brain—contribute to the survival, growth, and maintenance of neurons [218, 236] and participate in a variety of learning and memory functions [237].”
BackgroundPatten, A. R., Yau, S. Y., Fontaine, C. J., Meconi, A., Wortman, R. C., & Christie, B. R. (2015) · Brain Plasticity · doi:10.3233/bpl-150016 · Cited by 64 · see citing works
“tic plasticity and learning and memory [275, 276].”
Epigenetic regulation of estrogen-dependent memory
Fortress, A. M., & Frick, K. M. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.05.001 · Cited by 62 · see citing works
“The first evidence for a role of DNA methylation in regulating synaptic plasticity relating to memory came from reports examining in vitro regulation of brain derived neurotrophic factor (BDNF), a neurotrophin critical for hippocampal synaptic plasticity and memory (Cowansage et al., 2010).”
BackgroundBranca, C., Wisely, E. V., Hartman, L. K., Caccamo, A., & Oddo, S. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.011 · Cited by 61 · see citing works
Shukla, P. K., Meena, A. S., Dalal, K. K., Canelas, C., Samak, G., Pierre, J. F., & Rao, R. (2021) · Scientific Reports · doi:10.1038/s41598-020-80637-y · Cited by 64 · see citing works
Baek, S. (2016) · Journal of Exercise Rehabilitation · doi:10.12965/jer.1632808.404 · Cited by 61 · see citing works
“BDNF is a critical mediator for the beneficial effect of physical exercise on brain function because it supports neural survival, growth, and synaptic plasticity (Cowansage et al., 2010).”
BackgroundLi, C., Dabrowska, J., Hazra, R., & Rainnie, D. G. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026065 · Cited by 61 · see citing works
“Similarly, brain-derived neurotrophic factor (BDNF) has been implicated in many forms of synaptic plasticity associated with fear memory formation, including LTP [11,12].”
BackgroundBDNF controls object recognition memory reconsolidation
Radiske, A., Rossato, J. I., González, M. C., Köhler, C. A., Bevilaqua, L. R., & Cammarota, M. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.02.018 · Cited by 62 · see citing works
Barha, C. K., Best, J. R., Rosano, C., Yaffe, K. S., Catov, J. M., & Liu-Ambrose, T. Y. L. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz093 · Cited by 61 · see citing works
“BDNF is a neurotrophin critically involved in neuroplasticity, cellular mechanisms required for learning and memory, and is thought to mediate exercise efficacy in cognition (31).”
BackgroundEmerging Concepts and Functions of Autophagy as a Regulator of Synaptic Components and Plasticity
Liang, Y. (2019) · Cells · doi:10.3390/cells8010034 · Cited by 60 · see citing works
“Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family proteins, is an important regulator of long-term potentiation (LTP) in the hippocampus and in other brain regions [93,94].”
Backgroundde la Monte, S. M., Tong, M., Bowling, N., & Moskal, P. (2011) · Molecular Brain · doi:10.1186/1756-6606-4-13 · Cited by 56 · see citing works
“Both BDNF and NT3 are inhibited by ethanol [61], and their expression and function are intimately tied to insulin and IGF signal transduction cascades [77,78].”
BackgroundHwang, J., Castelli, D. M., & Gonzalez-Lima, F. (2017) · Physiology & Behavior · doi:10.1016/j.physbeh.2017.05.011 · Cited by 57 · see citing works
Distinct roles of prelimbic and infralimbic proBDNF in extinction of conditioned fear
Sun, W., Li, X., & An, L. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.12.018 · Cited by 56 · see citing works
“…been identified as playing a critical role in the acquisition and consolidation of hippocampal-mPFC dependent fear memory (Andero and Ressler, 2012; Cowansage et al., 2010; Rosas-Vidal et al., 2014) and was recently identified as involved in the extinction of fear memories (Andero and Ressler,…”
InfluentialControl of seizures by ketogenic diet-induced modulation of metabolic pathways
Clanton, R., Wu, G., Akabani, G., & Aramayo, R. (2016) · Amino Acids · doi:10.1007/s00726-016-2336-7 · Cited by 58 · see citing works
“BDNF plays a very important role in neuronal plasticity (Cowansage et al. 2010).”
BackgroundPeripheral toxicity in crack cocaine use disorders
Narvaez, J. C. D. M., Magalhães, P. V. D. S., Fries, G. R., Colpo, G. D., Czepielewski, L. S., Vianna, P., Chies, J. A. B., Rosa, A. R., DIEMEN, L. V., Vieta, E., et al. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.03.045 · Cited by 57 · see citing works
“[4] K.”
BackgroundDevelopmental Dyslexia: Environment Matters
Theodoridou, D., Christodoulides, P., Zakopoulou, V., & Syrrou, M. (2021) · Brain Sciences · doi:10.3390/brainsci11060782 · Cited by 59 · see citing works
A review of molecular genetic studies of neurocognitive deficits in schizophrenia
Zai, G. C., Robbins, T. W., Sahakian, B. J., & Kennedy, J. L. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.10.024 · Cited by 56 · see citing works
- Authors
- Cowansage, K., LeDoux, J., & Monfils, M.-H.
- Affiliations
- New York University (US)
- Venue
- Current Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2010-01-01
- Volume
- 3
- Issue
- 1
- Pages
- 12-29
- ISSN
- 1874-4672 (ISSN-L)
- OpenAlex
- W2158714604
- Cited by
- 372
- References
- 0
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 8 · 2023: 18 · 2022: 16 · 2021: 24 · 2020: 22 · 2019: 27 · 2018: 26 · 2017: 30 · 2016: 27 · 2015: 35 · 2014: 23 · 2013: 36 · 2012: 38
- FWCI
- 12.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain-derived neurotrophic factor, neuroplasticity, synaptic plasticity, neurotrophins, amygdala, hippocampus, emotional memory, maternal deprivation, environmental enrichment, epigenetic regulation, post-translational regulation, therapeutic target
- MeSH terms
- RE1-Silencing Transcription Factor, Hippocampus, Humans, Learning, Memory, Neuronal Plasticity, Repressor Proteins, Signal Transduction, Brain-Derived Neurotrophic Factor, Epigenesis, Genetic, Methyl-CpG-Binding Protein 2
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