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Cited by 284Nerve injury and regenerationTreatment of Major DepressionNeuroscience and Neuropharmacology Research

Neuronal plasticity and neurotrophic factors in drug responses

Open access
Castrén, E, Antila, H·2017·Molecular Psychiatry
DOI 10.1038/mp.2017.61PMC PMC5510719
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Abstract

Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors. Several clinically available drugs activate neurotrophin signaling and neuronal plasticity. In particular, antidepressant drugs rapidly activate TrkB signaling and gradually increase BDNF expression, and the behavioral effects of antidepressants are mediated by and dependent on BDNF signaling through TrkB at least in rodents. These findings indicate that antidepressants, widely used drugs, effectively act as TrkB activators. They further imply that neuronal plasticity is a central mechanism in the action of antidepressant drugs. Indeed, it was recently discovered that antidepressants reactivate a state of plasticity in the adult cerebral cortex that closely resembles the enhanced plasticity normally observed during postnatal critical periods. This state of induced plasticity, known as iPlasticity, allows environmental stimuli to beneficially reorganize networks abnormally wired during early life. iPlasticity has been observed in cortical as well as subcortical networks and is induced by several pharmacological and non-pharmacological treatments. iPlasticity is a new pharmacological principle where drug treatment and rehabilitation cooperate; the drug acts permissively to enhance plasticity and rehabilitation provides activity to guide the appropriate wiring of the plastic network. Optimization of iPlastic drug treatment with novel means of rehabilitation may help improve the efficacy of available drug treatments and expand the use of currently existing drugs into new indications.

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Cites

212 of 212 references verified0 citation errors · 0 not checkable

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Nothing to recompute.

Claims the paper makes

0 of 253 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    BDNF synthesis, release, and action are regulated by neuronal activity.

    “Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors.”
    • Also stated in: § Neurotrophins in Plasticity · plain
      “Subsequently, a similar activity-dependent regulation was observed for Bdnf mRNA39–41, and subsequent studies showed that synthesis and release of BDNF and NGF, but not those of NT-3 and NT-4, are regulated by activity9.”
    Quote in the paperSubstantial claim0 of 4 sources checked
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      Not checked in the free run.

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      Not checked in the free run.

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      Not checked in the free run.

    • cites [9] Poo MM . Neurotrophins as synaptic modulators. Nat Rev Neurosci 2001; 2: 24–32. source

      Not checked in the free run.

  • Premisecitation

    Neurotrophic factors, especially BDNF and other neurotrophins, centrally mediate activity-dependent plasticity that translates environmental experiences into neuronal structure and function.

    “Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks.”
    • Also stated in: § Introduction · hedged
      “To be translated into neuronal structure and function, neuronal activity needs molecular mediators9 and neurotropic factors are prime candidates for mediators between neuronal activity and plasticity10,11.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Poo MM . Neurotrophins as synaptic modulators. Nat Rev Neurosci 2001; 2: 24–32. source

      Not checked in the free run.

    • cites [10] Thoenen H . Neurotrophins and neuronal plasticity. Science 1995; 270: 593–598. source

      Not checked in the free run.

    • cites [11] Huang EJ, Reichardt LF . Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci 2001; 24: 677–736. source

      Not checked in the free run.

  • Premisecitation

    BDNF acting through its high-affinity TrkB receptors produces trophic effects including synapse formation, stabilization, and potentiation.

    “Synthesis, release and action of BDNF is regulated by neuronal activity and BDNF in turn leads to trophic effects such as formation, stabilization and potentiation of synapses through its high-affinity TrkB receptors.”
    • Also stated in: § Neurotrophins in Plasticity · plain
      “NGF and BDNF promote the outgrowth of axons and dendrites and increase synapse formation54–57.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [54] Cohen-Cory S, Fraser SE . Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature 1995; 378: 192–196. source

      Not checked in the free run.

    • cites [55] Mcallister AK, Lo DC, Katz LC . Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 1995; 15: 791–803. source

      Not checked in the free run.

    • cites [56] Mcallister AK, Katz LC, Lo DC . Neurotrophin regulation of cortical dendritic growth requires activity. Neuron 1996; 17: 1057–1064. source

      Not checked in the free run.

    • cites [57] Zagrebelsky M, Korte M . Form follows function: Bdnf and its involvement in sculpting the function and structure of synapses. Neuropharmacology 2014; 76: 628–638. source

      Not checked in the free run.

  • Premisecitation

    Antidepressants reactivate in the adult cerebral cortex a state of plasticity closely resembling that normally observed during postnatal critical periods.

    “Indeed, it was recently discovered that antidepressants reactivate a state of plasticity in the adult cerebral cortex that closely resembles the enhanced plasticity normally observed during postnatal critical periods.”
    • Also stated in: § Introduction · hedged
      “However, recent data indicate that several drugs used for the treatment of neuropsychiatric disorders can directly influence the plasticity and reactivate a critical period-like plasticity in the adult brain, a process known as induced plasticity (iPlasticity)5–8.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [5] Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O’leary OF et al. The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science 2008; 320: 385–388. source

      Not checked in the free run.

    • cites [6] Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T et al. Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci USA 2010; 107: 8434–8439. source

      Not checked in the free run.

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      Not checked in the free run.

  • Premisereasoning

    Several clinically available drugs directly activate neurotrophins and neuronal plasticity.

    “Several clinically available drugs directly activate neurotrophins and neuronal plasticity.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 6
  • May combine two claims. 18

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    iPlasticity constitutes a pharmacological principle in which drug treatment and rehabilitation cooperate, with the drug permissively enhancing plasticity and rehabilitation guiding network wiring.

    “iPlasticity is a new pharmacological principle where drug treatment and rehabilitation cooperate: the drug acts permissively to enhance plasticity and rehabilitation provides activity to guide the appropriate wiring of the plastic network.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Neuronal plasticity includes both trophic processes such as neurogenesis and synaptogenesis and atrophic processes such as elimination of inactive neurons and contacts.

    “Neuronal plasticity does not only involve trophic processes such as neurogenesis and synaptogenesis, but also includes atrophic processes, such as the elimination of inactive neurons and neuronal contacts.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1] Katz LC, Shatz CJ . Synaptic activity and the construction of cortical circuits. Science 1996; 274: 1133–1138. source

      Not checked in the free run.

    • cites [2] Holtmaat A, Caroni P . Functional and structural underpinnings of neuronal assembly formation in learning. Nat Neurosci 2016; 19: 1553–1562. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NGF and BDNF were discovered because they support the survival of neurons and neurites during development.

    “The first neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were discovered through their ability to support the survival of neurons and neurites during development15–17; other members of the neurotrophin family, neurotrophin-3 (NT-3)18–20 and neurotrophin-4 (NT-4)21–23 were then identified through sequence similarity to NGF and BDNF.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [15] Levi-Montalcini R, Cohen S . In vitro and in vivo effects of a nerve growth-stimulating agent isolated from snake venom. Proc Natl Acad Sci USA 1956; 42: 695–699. source

      Not checked in the free run.

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      Not checked in the free run.

    • cites [17] Barde YA . Trophic factors and neuronal survival. Neuron 1989; 2: 1525–1534. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Plasticity has no inherent direction; experience-dependent activity within the network determines which connections are strengthened and maintained and which are eliminated.

    “Therefore, plasticity in itself does not have any particular direction; it is the experience-dependent activity within the neuronal network that determines which of the connections are strengthened and maintained and which ones are eliminated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Plasticity is adaptive when guided by beneficial environmental stimuli but can be maladaptive when guiding experiences are adverse.

    “Therefore, plasticity is adaptive when it is guided by beneficial environmental stimuli, but it can also be maladaptive, if the guiding experiences are adverse.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NT-3 and NT-4 were identified by sequence similarity to NGF and BDNF.

    “The first neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were discovered through their ability to support the survival of neurons and neurites during development15–17; other members of the neurotrophin family, neurotrophin-3 (NT-3)18–20 and neurotrophin-4 (NT-4)21–23 were then identified through sequence similarity to NGF and BDNF.”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [18] Hohn A, Leibrock J, Bailey K, Barde YA . Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature 1990; 344: 339–341. source

      Not checked in the free run.

    • cites [19] Ernfors P, Ibanez CF, Ebendal T, Olson L, Persson H . Molecular cloning and neurotrophic activities of a protein with structural similarities to nerve growth factor: developmental and topographical expression in the brain. Proc Natl Acad Sci USA 1990; 87: 5454–5458. source

      Not checked in the free run.

    • cites [20] Maisonpierre PC, Belluscio L, Squinto S, Ip NY, Furth ME, Lindsay RM et al. Neurotrophin-3: a neurotrophic factor related to ngf and bdnf. Science 1990; 247: 1446–1451. source

      Not checked in the free run.

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      Not checked in the free run.

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      Not checked in the free run.

    • cites [23] Ip NY, Ibanez CF, Nye SH, Mcclain J, Jones PF, Gies DR et al. Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci USA 1992; 89: 3060–3064. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NGF binds TrkA, BDNF and NT-4 bind TrkB, NT-3 mainly interacts with TrkC, and all neurotrophin family members bind p75NTR.

    “NGF binds to TrkA, BDNF and NT-4 to TrkB and NT-3 interacts mainly with TrkC receptors, whereas all neurotrophin family members bind to the p75NTR32.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Chao MV . Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat.Rev.Neurosci 2003; 4: 299–309. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NGF and BDNF promote axon and dendrite outgrowth.

    “NGF and BDNF promote the outgrowth of axons and dendrites and increase synapse formation54–57.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [54] Cohen-Cory S, Fraser SE . Effects of brain-derived neurotrophic factor on optic axon branching and remodelling in vivo. Nature 1995; 378: 192–196. source

      Not checked in the free run.

    • cites [55] Mcallister AK, Lo DC, Katz LC . Neurotrophins regulate dendritic growth in developing visual cortex. Neuron 1995; 15: 791–803. source

      Not checked in the free run.

    • cites [56] Mcallister AK, Katz LC, Lo DC . Neurotrophin regulation of cortical dendritic growth requires activity. Neuron 1996; 17: 1057–1064. source

      Not checked in the free run.

    • cites [57] Zagrebelsky M, Korte M . Form follows function: Bdnf and its involvement in sculpting the function and structure of synapses. Neuropharmacology 2014; 76: 628–638. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BDNF promotes synaptic transmission and LTP in vitro and in vivo.

    “Furthermore, BDNF increases neurotransmitter release62, promotes synaptic transmission and LTP in vitro63–65 as well as in vivo66–69.”
    Quote in the paperNot a substantial claim0 of 7 sources checked
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      Not checked in the free run.

    • cites [64] Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B . Regulation of synaptic responses to high-frequency stimulation and ltp by neurotrophins in the hippocampus. Nature 1996; 381: 706–709. source

      Not checked in the free run.

    • cites [65] Lessmann V, Gottmann K, Heumann R . Bdnf and nt-4/5 enhance glutamatergic synaptic transmission in cultured hippocampal neurones. NeuroReport 1994; 6: 21–25. source

      Not checked in the free run.

    • cites [66] Messaoudi E, Bardsen K, Srebro B, Bramham CR . Acute intrahippocampal infusion of bdnf induces lasting potentiation of synaptic transmission in the rat dentate gyrus. J Neurophysiol 1998; 79: 496–499. source

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    • cites [67] Panja D, Kenney JW, D’andrea L, Zalfa F, Vedeler A, Wibrand K et al. Two-stage translational control of dentate gyrus LTP consolidation is mediated by sustained BDNF-TrkB signaling to mnk. Cell Rep 2014; 9: 1430–1445. source

      Not checked in the free run.

    • cites [68] Panja D, Bramham CR . Bdnf mechanisms in late ltp formation: a synthesis and breakdown. Neuropharmacology 2014; 76: 664–676. source

      Not checked in the free run.

    • cites [69] Kuipers SD, Trentani A, Tiron A, Mao X, Kuhl D, Bramham CR . Bdnf-induced ltp is associated with rapid arc/arg3.1-dependent enhancement in adult hippocampal neurogenesis. Sci Rep 2016; 6: 21222. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TrkB-deficient mice show blunted LTP and deficient learning.

    “Mice deficient in TrkB also show blunted LTP and deficient learning58,78.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] Minichiello L . Trkb signalling pathways in ltp and learning. Nat Rev Neurosci 2009; 10: 850–860. source

      Not checked in the free run.

    • cites [78] Minichiello L, Korte M, Wolfer D, Kuhn R, Unsicker K, Cestari V et al. Essential role for trkb receptors in hippocampus-mediated learning. Neuron 1999; 24: 401–414. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Direct current stimulation promotes learning in homozygous BDNF val/val subjects but not in met allele carriers, both in humans and mice.

    “Consistent with this, direct current stimulation promotes learning in homozygous BDNF val/val subjects, but not in met allele carriers, both in humans and mice76.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Fritsch B, Reis J, Martinowich K, Schambra HM, Ji Y, Cohen LG et al. Direct current stimulation promotes bdnf-dependent synaptic plasticity: potential implications for motor learning. Neuron 2010; 66: 198–204. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There have been efforts to use BDNF as a therapeutic agent for neuropsychiatric disorders or to develop small molecules that increase BDNF production or activate TrkB in the brain.

    “Since the discovery of BDNF and its receptor TrkB, efforts have been made to use BDNF as a therapeutic agent for neuropsychiatric disorders or to develop small-molecule pharmaceuticals that could increase the production of BDNF or activate TrkB in brain (for review, see99,100), and these efforts are still ongoing101.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chronic fluoxetine treatment reactivates juvenile-like plasticity, and monocular deprivation then shifts ocular dominance in adult rat visual cortex.

    “During chronic treatment by fluoxetine, critical period-like plasticity is reactivated and monocular deprivation induces a shift in ocular dominance in the visual cortex of adult rats5”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O’leary OF et al. The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science 2008; 320: 385–388. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    Intracortical ChABC infusion is invasive and cannot be used in humans.

    “Intracortical infusion of ChABC is an invasive procedure and not feasible for human use.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Chronic oral fluoxetine induces markers of juvenile-like plasticity and promotes LTP in the amygdala.

    “Chronic peroral fluoxetine exposure induces markers of critical period-like plasticity and promotes LTP in the amygdala”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [143] Karpova NN, Pickenhagen A, Lindholm J, Tiraboschi E, Kulesskaya N, Agustsdottir A et al. Fear erasure in mice requires synergy between antidepressant drugs and extinction training. Science 2011; 334: 1731–1734. source

      Not checked in the free run.

    • cites [196] Yang EJ, Lin EW, Hensch TK . Critical period for acoustic preference in mice. Proc Natl Acad Sci USA 2012; 109: 17213–17220. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fluoxetine increases structural plasticity in mouse visual cortex and promotes turnover of synaptic sites.

    “Fluoxetine has also been shown to produce enhanced structural plasticity in the mouse visual cortex, promoting turnover of synaptic sites141.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [141] Chen JL, Lin WC, Cha JW, So PT, Kubota Y, Nedivi E . Structural basis for the role of inhibition in facilitating adult brain plasticity. Nat Neurosci 2011; 14: 587–594. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Fluoxetine can reactivate juvenile-like plasticity in many cortical regions and restore vision in an amblyopic eye in adult rodents.

    “these data demonstrate that a safe and widely used drug fluoxetine can reactivate critical period-like plasticity in many cortical regions and promote recovery of vision in an amblyopic eye in adult rodents”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Fluoxetine promotes recovery from stroke and brain trauma.

    “Fluoxetine has recently been found to promote recovery from stroke and from brain trauma198–200.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [198] Maya-Vetencourt JF, Baroncelli L, Viegi A, Tiraboschi E, Castrén E, Cattaneo A et al. Igf-1 restores visual cortex plasticity in adult life by reducing local gaba levels. Neural Plast 2012; 2012: 250421.

      Not checked in the free run.

    • cites [199] Sale A, Maya Vetencourt JF, Medini P, Cenni MC, Baroncelli L, De Pasquale R et al. Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition. Nat Neurosci 2007; 10: 679–681. source

      Not checked in the free run.

    • cites [200] Greifzu F, Pielecka-Fortuna J, Kalogeraki E, Krempler K, Favaro PD, Schluter OM et al. Environmental enrichment extends ocular dominance plasticity into adulthood and protects from stroke-induced impairments of plasticity. Proc Natl Acad Sci USA 2014; 111: 1150–1155. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HDAC inhibition increases expression of plasticity-related factors and promotes ocular dominance plasticity in the visual cortex.

    “HDAC inhibition increases the expression of plasticity-related factors and promotes OD plasticity in the visual cortex194,205,206.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [194] Putignano E, Lonetti G, Cancedda L, Ratto G, Costa M, Maffei L et al. Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity. Neuron 2007; 53: 747–759. source

      Not checked in the free run.

    • cites [205] Acler M, Robol E, Fiaschi A, Manganotti P . A double blind placebo rct to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients. J Neurol 2009; 256: 1152–1158. source

      Not checked in the free run.

    • cites [206] Jorge RE, Acion L, Moser D, Adams HPJ, Robinson RG . Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry 2010; 67: 187–196. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Physostigmine induces ocular dominance plasticity in adult mouse visual cortex and reverses amblyopia in adulthood when given with patching of the better eye.

    “The cholinesterase inhibitor physostigmine was recently demonstrated to induce OD plasticity in the adult mouse visual cortex and to reverse amblyopia in adulthood when given together with patching of the better eye210”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [210] Karpova NN . Role of bdnf epigenetics in activity-dependent neuronal plasticity. Neuropharmacology 2014; 76 (Pt C): 709–718. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    iPlasticity induced by fluoxetine and by an enriched environment closely resemble each other and share electrophysiological properties with the natural critical period.

    “iPlasticity induced by fluoxetine and enriched environment closely resemble each other and they both share electrophysiological properties with the naturally occurring critical period.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    iPlastic drugs must be combined with rehabilitation to guide plastic networks toward a new function.

    “iPlastic drugs need to be combined with rehabilitation to guide the plastic networks towards a new function.”
    Quote in the paperNot a substantial claim
22 of 22

  • The paper relies on this without support.

    Plasticity driven by activity depends on new gene expression and protein synthesis.

    “Since activity-dependent plasticity requires changes in gene expression and protein synthesis, HDAC inhibitors might activate iPlasticity.”

  • The paper relies on this without support.

    Perfect pitch develops during a postnatal critical period.

    “since development of perfect pitch has a postnatal critical period”

  • The paper relies on this without support.

    Critical periods are ubiquitous.

    “the fact that critical periods are ubiquitous”

  • The paper relies on this without support.

    Histone acetylation is a key epigenetic mechanism that promotes open chromatin and regulates gene expression.

    “Histone acetylation is one of the key epigenetic mechanisms promoting the open chromatin state and regulating gene expression.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Induced plasticity (iPlasticity) has been hypothesized to play a major role in the actions of essentially all antidepressant treatments including slow-acting traditional antidepressants, transcranial magnetic stimulation, electroconvulsive therapy, exercise, and acute sleep deprivation.

    “Such induced plasticity (iPlasticity) (14) has been hypothesized to play a major role in the actions of essentially all antidepressant treatments including slow-acting traditional antidepressants (15), transcranial magnetic stimulation (16), electroconvulsive therapy (15, 17), exercise (18), and acute sleep deprivation (19).”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [14]

  • BDNF synthesis in the visual cortex is regulated by visual stimulation.

    “The observation that BDNF synthesis in the visual cortex is regulated by visual stimulation made BDNF the prime candidate for this activity-dependent regulated factor [163,164,165].”

    From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [164]

  • Increasing evidence suggests that BDNF-TrkB signaling underlies a substantial portion of both affective pathophysiology and treatment response across therapeutic approaches.

    “Increasing evidence suggests that BDNF-TrkB signaling underlies a substantial portion of both affective pathophysiology and treatment response across therapeutic approaches [51,52].”

    From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [51]

  • In adult rats, chronic treatment with the SSRI fluoxetine has been shown to reactivate a critical period-like plasticity in the visual cortex.

    “in adult rats, chronic treatment with the SSRI fluoxetine has been shown to reactivate a critical period-like plasticity in the visual cortex [13, 14].”

    From Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial (2023) · cites this paper as [14]

  • BDNF is known to have antidepressant effects and is increased in response to SSRIs.

    “BDNF is known to have antidepressant effects and is increased in response to SSRIs, which forms a strong link between SSRIs and neuroplasticity [14].”

    From Effects of escitalopram on synaptic density in the healthy human brain: a randomized controlled trial (2023) · cites this paper as [14]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Castrén E, Maya-Vetencourt JF . Neurotrophins as regulators of visual cortcal plasticity. In: Chalupa LM, Berardi N, M C, Galli-Resta L, Pizzorusso T (eds). Cerebral Plasticity. MIT Press: Cambridge, MA, USA, 2011, pp 343–354. · DOI

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Authors
Castrén, E., & Antila, H.
Affiliations
University of Helsinki (FI)
ORCID
Antila, H
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-04-11
Volume
22
Issue
8
Pages
1085-1095
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2017.61
PMC
PMC5510719
OpenAlex
W2607000919
Cited by
284
References
212
Citations by year
2026: 33 · 2025: 37 · 2024: 29 · 2023: 37 · 2022: 31 · 2021: 30 · 2020: 27 · 2019: 28 · 2018: 28 · 2017: 3
FWCI
11.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion, other-oa)
Funders
Sigrid Juséliuksen Säätiö (307416, 322742)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
neuroplasticity, neurotrophic factors, brain-derived neurotrophic factor, TrkB receptor, antidepressants, activity-dependent plasticity, neurotrophin signaling, synaptic potentiation, rehabilitation, cortical reorganization
MeSH terms
Animals, Antidepressive Agents, Cerebral Cortex, Depressive Disorder, Humans, Nerve Growth Factors, Neuronal Plasticity, Signal Transduction, Brain-Derived Neurotrophic Factor, Receptor, trkB

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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