Cited by 372Nerve injury and regenerationNeurogenesis and neuroplasticity mechanismsNeuroscience and Neuropharmacology Research

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Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity.

Cowansage, Kiriana, LeDoux, Joseph, Monfils, Marie-H.·2010·Current Molecular Pharmacology

DOI 10.2174/1874467211003010012

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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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Background
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Background
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Background
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BackgroundInfluential
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Background
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Background
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Background
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Result
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Background
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BackgroundInfluential
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Background
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Background
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Background
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Background
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Background
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“As BDNF is a crucial modulator of synaptic plasticity, its proper function is of relevance for cognitive functions [21,22].”
Background
Innate BDNF expression is associated with ethanol intake in alcohol-preferring AA and alcohol-avoiding ANA rats
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“NTFs are important factors influencing neuronal plasticity following nerve injury [16].”
Background
Impact of Chronic BDNF Depletion on GABAergic Synaptic Transmission in the Lateral Amygdala
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“BDNF is first expressed in a pro-form (pBDNF) that binds the p75 receptor and triggers neuronal apoptosis [62].”
Background
Continuous administration of a p38α inhibitor during the subacute phase after transient ischemia-induced stroke in the rat promotes dose-dependent functional recovery accompanied by increase in brain BDNF protein level
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“Reduced BDNF levels occur in AD, which may cause the progressive neuronal atro phy observed in affected brain regions ( 85 , 86 ).”
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Current Neurogenic and Neuroprotective Strategies to Prevent and Treat Neurodegenerative and Neuropsychiatric Disorders
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Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice
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“This profile appears in line with the modulatory effect exerted by nicotine treatment, since it is well known that BDNF expression is dynamically modulated by epigenetic modifications (Cowansage et al. 2010; Roth and Sweatt 2011).”
Background
Inhibition of PirB Activity by TAT-PEP Improves Mouse Motor Ability and Cognitive Behavior
Mi, Y., Chen, H., Guo, N., Sun, M.-Y., Zhao, Z., Gao, X., Wang, X., Zhang, R., Zhou, J., & Gou, X. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00199 · Cited by 12
“…treatment might be mediated by BDNF. BDNF is known to play an important role in the regulation of learning and memory (Komulainen et al., 2008; Cowansage et al., 2010; Lu et al., 2014; Tong et al., 2015), and can be used as a therapeutic agent to alleviate cognitive impairment (Wu et al.,…”
Background
BDNF Val66Met, stress, and positive mothering: Differential susceptibility model of adolescent trait anxiety
Chen, J., Yu, J., Liu, Y., Zhang, L., & Zhang, J. (2015) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2015.06.001 · Cited by 12
Fasting plasma peptide YY concentrations are increased in patients with major depression who associate weight loss.
Giménez‐Palop, O., Coronas, R., Cobo, J., Gallart, L., Barbero, J. D., Parra, I., Fuste, G., Vendrell, J. J., Bueno, M., González-Clemente, J. M., et al. (2012) · PubMed · doi:10.3275/8180 · Cited by 12
“BDNF is a potent modulator of synaptic plasticity and contributes to the central control of food intake as an anorexigenic factor (4, 5).”
Background
Putative pathological mechanisms of late-life depression and Alzheimer’s disease
Hasan, S. M. N., Clarke, C., Strand, T., & Bambico, F. R. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148423 · Cited by 13
Exercise Maintains Dendritic Complexity in an Animal Model of Posttraumatic Stress Disorder
Hoffman, J. R., Cohen, H., Ostfeld, I., Kaplan, Z., Zohar, J., & Cohen, H. (2016) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001038 · Cited by 12
“The increase in the expression of BDNF after endurance training is reported to stimulate an increase in dendritic spine density and dendritic arborization (7,23,25).”
Background
Alleviation of Catching and Crating Stress by Dietary Supplementation of Bacillus subtilis in Pekin Ducks
Mitin, H., ZULKIFLI, I., Jamri, M. H. C., et al. (2022) · Animals · doi:10.3390/ani12243479 · Cited by 11
“It can increase neuroplasticity, aid in nerve development and differentiation, and directly impact cognitive processes, including memory and adaptability in the brain [57].”
Background
Natural essential oils derived from herbal medicines: A promising therapy strategy for treating cognitive impairment
Shi, A., Long, Y., Ma, Y., Yu, S., Li, D., Deng, J., Wen, J., Li, X., Wu, Y., He, X., et al. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1104269 · Cited by 13
Mania: Not the opposite of depression, but an extension? Neuronal plasticity and polarity
Mizuno, T., Omata, N., Murata, T., Mitsuya, H., Maruoka, N., Mita, K., Kiyono, Y., Okazawa, H., Ikeda, H., & Wada, Y. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.05.012 · Cited by 11
“As is often reported, brain-derived neurotrophic factor (BDNF) is deeply related to neuronal plasticity [28,29].”
Background
Effects of exercise on mature or precursor brain-derived neurotrophic factor pathways in ovariectomized rats
Park, J.-K., Hong, Y.-P., & Lee, S. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6614 · Cited by 12
“…of mBDNF induced by OVX. mBDNF exerts its actions on neuronal structure, function and synaptic plasticity underlying memory and cognition (41-43) by activation of MAPK, PI3K-Akt, PLC γ , Ca 2+ /calmodulin-dependent protein kinase and cAMP response element-binding protein pathways…”
Housing and road transport modify the brain neurotransmitter systems of pigs: Do pigs raised in different conditions cope differently with unknown environments?
Arroyo, L., Valent, D., Carreras, R., Peña, R., Sabrià, J., Velarde, A., & Bassols, A. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210406 · Cited by 11
Amygdalohippocampal neuroplastic changes following neuroleptic treatment with quetiapine in first-episode schizophrenia
Poeppl, T. B., Frank, E., Schecklmann, M., Kreuzer, P. M., Prasser, S. J., Rupprecht, R., Hajak, G., Langguth, B., & Landgrebe, M. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713001739 · Cited by 12
“Recently, there is growing empirical support for BDNF-dependent modulation of neural plasticity in the amygdala (Cowansage et al., 2010).”
Background
Leishmania amazonensis infection induces behavioral alterations and modulates cytokine and neurotrophin production in the murine cerebral cortex
Portes, A., Giestal‐de‐Araujo, E., Fagundes, A., Pandolfo, P., Geraldo, A. D. S., Lira, M.-L. F., Amaral, V. F., & Lagrota-Cândido, J. (2016) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2016.11.003 · Cited by 12
“Moreover, low levels of this cytokine are associated with Parkinson's disease and Huntington's disease (Autry and Monteggia, 2012; Baquet et al., 2005; Cowansage et al., 2010) indicating an important role for this neurotrophin in the development as well as in adult life.”
Background
Electro-acupuncture-induced neuroprotection is associated with activation of the IGF-1/PI3K/Akt pathway following adjacent dorsal root ganglionectomies in rats
Hu, T., Lu, M., Chen, B., Tong, J., Mao, R., Li, S., Dai, P., Tan, Y., & Xiyang, Y. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.4035 · Cited by 10
“NTFs are important factors that influence neuronal plasticity following nerve injury (12).”
BackgroundInfluential
Bicarbonate supplementation via lactate efflux improves anaerobic and cognitive performance in elite combat sport athletes
Chycki, J., Zając, A., & Toborek, M. J. (2021) · Biology of Sport · doi:10.5114/biolsport.2020.96320 · Cited by 11
The Effect of Electroacupuncture versus Manual Acupuncture through the Expression of TrkB/NF‐κB in the Subgranular Zone of the Dentate Gyrus of Telomerase‐Deficient Mice
Lin, D., Zhang, J., Zhuang, W., Yan, X., Yang, X., Lin, S., & Lin, L. (2018) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2018/1013978 · Cited by 10
Mitigation of oxidative stress with dihydroactinidiolide, a natural product against scopolamine-induced amnesia in Swiss albino mice
Das, M., Balan, D. J., & Devi, K. P. (2021) · NeuroToxicology · doi:10.1016/j.neuro.2021.08.003 · Cited by 11
Brain-Derived Neurotrophic Factor-Mediated Cognitive Impairment in Hypothyroidism
Umesh, M., Kalpana, M., Singaravelu, V., Ganji, V., John, N. A., & Archana Gaur, T. (2022) · Cureus · doi:10.7759/cureus.23722 · Cited by 10
“Both the transcription of the BDNF gene and the transport of BDNF mRNA and protein into the dendrites are regulated by neuronal activity, which might also encompass the activation of presynaptic N-methyl-Daspartate (NMDA) glutamate receptors [30-31].”
Background
Hippocampal and amygdalar increased BDNF expression in the extinction of opioid-induced place preference
Lloret-Torres, M. E., Ayala-Pagán, R. N., Martínez-Rivera, F. J., Bonilla-Rullán, P., & Barreto-Estrada, J. L. (2022) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2022.10.007 · Cited by 9
“The dorsal HPC also may be involved in addiction processes given its dense connections to the VS/NAc and its associations with behavioral sensitization (Degoulet et al., 2008).”
Background
Brain-derived neurotrophic factor prevents beta- amyloid-induced apoptosis of pheochromocytoma cells by regulating Bax/Bcl-2 expression.
Sun, Z., Ma, X., Yang, H., Zhao, J., & Zhang, J. (2012) · Europe PMC (PubMed Central) · doi:10.3969/j.issn.1673-5374.2012.05.004 · Cited by 10
“It regulates synaptic plasticity and plays a key role in memory formation and storage [13] .”
Background
Balinese Cultivar of Purple Sweet Potato Improved Neurological Score and BDNF and Reduced Caspase-Independent Apoptosis among Wistar Rats with Ischemic Stroke
Adnyana, I. M. O., Sudewi, R., Samatra, P., et al. (2019) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2019.019 · Cited by 10
TBI and sex: Crucial role of progesterone protecting the brain in an omega−3 deficient condition
Tyagi, E., Agrawal, R., Ying, Z., & Gómez‐Pinilla, F. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.12.004 · Cited by 11
“The effect of hormonal treatment (F1,20 = 17.818, p 0.01) and its interaction (F1,20 = 10.612, p 0.01) with injury was significant for the levels of BDNF as analyzed by two-way ANOVA.”
BackgroundInfluential
The Three Neurogenetic Phases of Human Consciousness
Grandy, J. K. (2013) · CIIS Digital Commons (California Institute of Integral Studies) · Cited by 9
Maintenance of postsynaptic neuronal excitability by a positive feedback loop of postsynaptic BDNF expression
Hao, L., Yang, Z., Gong, P., & Lei, J. (2018) · Cognitive Neurodynamics · doi:10.1007/s11571-018-9479-z · Cited by 9
“Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of growth factors that facilitate neuronal survival and development, is a key regulator of synaptic plasticity (McAllister et al. 1999; Lu 2003; Li et al. 2013; Bramham and Messaoudi 2005; Cowansage et al. 2010; Edelmann et al. 2014).”
Background
Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users
Roviš, D., Černelič-Bizjak, M., Vasiljev, V., Petelin, A., Jenuš, T., Vidic, S., Drevenšek, G., & Pražnikar, Z. J. (2018) · European Addiction Research · doi:10.1159/000492582 · Cited by 10
Effects of Genistein and Exercise Training on Brain Damage Induced by a High‐Fat High‐Sucrose Diet in Female C57BL/6 Mice
Li, R., Ding, X.-W., Geetha, T., Fadamiro, M., Aubin, C. R. S., Shim, M., Al‐Nakkash, L., Broderick, T. L., & Babu, J. R. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1560435 · Cited by 9
“Brain-derived neurotrophic factor (BDNF), a key molecule involved in synapse function and neurite growth, is emerging as a crucial player in synaptic plasticity, learning, and memory [27].”
Importance of selected genetic determinants on endurance performance and physical strength: a narrative review
Yao, J., Saraf, F., Rathore, V. S., Darkazanli, K., Liu, Y., Korivi, M., & Bhaskar, L. V. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1568334 · Cited by 9
“Brain derived neurotrophic factor (BDNF) belongs to the neurotrophin family of growth factors that promotes neural plasticity linked to learning, memory, and recovery from brain injury (Numakawa and Kajihara, 2025; Cowansage et al., 2010).”
Development of Precision Small-Molecule Proneurotrophic Therapies for Neurodegenerative Diseases
Janssens, J., Lu, D., Ni, B., Chadwick, W., Siddiqui, S., Azmi, A. S., Etienne, H., Jushaj, A., van Gastel, J., Martin, B., et al. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2016.10.006 · Cited by 8
Role of brain-derived neurotrophic factor in shaping the behavioural response to environmental stressors
Badowska‐Szalewska, E., Lietzau, G., Moryś, J., & Kowiański, P. (2021) · Folia Morphologica · doi:10.5603/fm.a2021.0079 · Cited by 8
“Consequently, BDNF has a role in promoting learning, cognitive and memory skills, as well as reduction of anxiety [37, 38].”
Background
Association Analysis of Polymorphic Variants of the BDNF Gene in Athletes
Niewczas, M., Król, P., Czarny, W., Bajorek, W., Rzepko, M., Drozd, S., Płonka, A., Drozd, M., Czaja, R., Błach, W., et al. (2021) · Genes · doi:10.3390/genes12091340 · Cited by 8
“Conscientiousness as a phenotype expressed with behavior might be conditioned with polymorphic variants of genes connected to neurotransmission [2].”
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A novel analog of olanzapine linked to sarcosinyl moiety (PGW5) demonstrates high efficacy and good safety profile in mouse models of schizophrenia
Gil‐Ad, I., Portnoy, M., Tarasenko, I., Bidder, M., Kramer, M., Taler, M., & Weizman, A. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.11.009 · Cited by 8
“Brain derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the CNS and its expression in the prefrontal cortex (PFC) and hippocampus is high (Cowansage et al., 2010) and has been shown to have long-term effects on neuronal survival, differentiation and synaptic plasticity (Park and Poo, 20…”
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Aerobic exercise ameliorates learning and memory deficits of aging rats induced by D-galactose via promoting SYP and BNDF expression in hippocampus
Fu, Y. H. H., Zhang, Y., & Yuan, Q. (2017) · BIO Web of Conferences · doi:10.1051/bioconf/20170801020 · Cited by 8
“It is generally acknowledged that synapse is the key structure of neuron networking and information transmission and that neuronal synaptic plasticity is the important part of neurobiology for learning and memory ability[10,11].”
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Study on the mechanism of Dexmedetomidine’s effect on postoperative cognitive dysfunction in elderly people
Cai, Y., Fan, Y., Wu, W., & Chen, W. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1508661 · Cited by 8
“Among these, BDNF, a direct target gene of CREB, plays a pivotal role in synaptic plasticity and memory formation (Lee and Silva, 2009; Cowansage et al., 2010; Miranda et al., 2019).”
Determinants of Cortical Synchrony
Mongrain, V., & Warby, S. C. (2012) · SLEEP · doi:10.5665/sleep.1680 · Cited by 7
Applications of the Neonatal Quinpirole Model to Psychosis and Convergence upon the Dopamine D2 Receptor
Brown, R. W., & Peterson, D. J. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_394 · Cited by 8
The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor (BDNF) in Individuals with Mild Cognitive Impairment: a Systematic Review and Meta-Analysis of a Randomized Controlled Trials
Kim, H., Lee, D., & Lee, Y. (2022) · Physical therapy rehabilitation science · doi:10.14474/ptrs.2022.11.3.304 · Cited by 13
Sex and BDNF Val66Met polymorphism matter for exercise-induced increase in neurogenesis and cognition in middle-aged mice
Islas-Preciado, D., Splinter, T. F. L., Ibrahim, M., Black, N., Wong, S. J., Lieblich, S. E., Liu-Ambrose, T. Y. L., Barha, C. K., & Galea, L. A. M. (2023) · Hormones and Behavior · doi:10.1016/j.yhbeh.2022.105297 · Cited by 6

Authors: Cowansage, K., LeDoux, J., & Monfils, M.-H.
Affiliations: New York University (US)
ORCID: Cowansage, Kiriana
LeDoux, Joseph
Monfils, Marie-H.
Venue: Current Molecular Pharmacology
Publisher: Elsevier BV
Published: 2010-01-01
Volume: 3
Issue: 1
Pages: 12-29
ISSN: 1874-4672 (ISSN-L)
DOI: 10.2174/1874467211003010012
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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Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity.

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