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Brain-derived neurotrophic factor

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BDNF
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBDNF, brain-derived neurotrophic factor, ANON2, BULN2, Brain-derived neurotrophic factor, brain derived neurotrophic factor
External IDsOMIM: 113505; MGI: 88145; HomoloGene: 7245; GeneCards: BDNF; OMA:BDNF - orthologs
Orthologs
SpeciesHumanMouse
Entrez

627

12064

Ensembl

ENSG00000176697

ENSMUSG00000048482

UniProt

P23560

P21237

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 11: 27.65 – 27.72 MbChr 2: 109.51 – 109.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Brain-derived neurotrophic factor (BDNF), or abrineurin,[5] is a protein[6] that, in humans, is encoded by the BDNF gene.[7][8] BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen.[9]

BDNF activates the TrkB tyrosine kinase receptor.[10][11]

Function

[edit]

BDNF acts on certain neurons of the central nervous system and the peripheral nervous system expressing TrkB, helping to support survival of existing neurons, and encouraging growth and differentiation of new neurons and synapses.[12][13] In the brain it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking.[14] BDNF is also expressed in the retina, kidneys, prostate, motor neurons, and skeletal muscle, and is also found in saliva.[15][16]

BDNF itself is important for long-term memory.[17] Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells in a process known as neurogenesis. Neurotrophins are proteins that help to stimulate and control neurogenesis, BDNF being one of the most active.[18][19][20] Mice born without the ability to make BDNF have developmental defects in the brain and sensory nervous system, and usually die soon after birth, suggesting that BDNF plays an important role in normal neural development.[21] Other important neurotrophins structurally related to BDNF include NT-3, NT-4, and NGF.

BDNF is made in the endoplasmic reticulum and secreted from dense-core vesicles. It binds carboxypeptidase E (CPE), and disruption of this binding has been proposed to cause the loss of sorting BDNF into dense-core vesicles. The phenotype for BDNF knockout mice can be severe, including postnatal lethality. Other traits include sensory neuron losses that affect coordination, balance, hearing, taste, and breathing. Knockout mice also exhibit cerebellar abnormalities and an increase in the number of sympathetic neurons.[22]

Certain types of physical exercise have been shown to markedly (threefold) increase BDNF synthesis in the human brain, a phenomenon which is partly responsible for exercise-induced neurogenesis and improvements in cognitive function.[16][23][24][25][26] Niacin appears to upregulate BDNF and tropomyosin receptor kinase B (TrkB) expression as well.[27]

Mechanism of action

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BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkB (pronounced "Track B")[10][11] and the LNGFR (for low-affinity nerve growth factor receptor, also known as p75).[28] It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor.[29] BDNF has also been shown to interact with the reelin signaling chain.[30] The expression of reelin by Cajal–Retzius cells goes down during development under the influence of BDNF.[31] The latter also decreases reelin expression in neuronal culture.

TrkB

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The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and TrkC. TrkB autophosphorylation is dependent upon its ligand-specific association with BDNF,[10][11] a widely expressed activity-dependent neurotrophic factor that regulates plasticity and is dysregulated following hypoxic injury. The activation of the BDNF-TrkB pathway is important in the development of short-term memory and the growth of neurons.[citation needed]

LNGFR

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The role of the other BDNF receptor, p75, is less clear. While the TrkB receptor interacts with BDNF in a ligand-specific manner, all neurotrophins can interact with the p75 receptor.[32] When the p75 receptor is activated, it leads to activation of NFkB receptor.[32] Thus, neurotrophic signaling may trigger apoptosis rather than survival pathways in cells expressing the p75 receptor in the absence of Trk receptors. Recent studies have revealed a truncated isoform of the TrkB receptor (t-TrkB) may act as a dominant negative to the p75 neurotrophin receptor, inhibiting the activity of p75, and preventing BDNF-mediated cell death.[33]

Expression

[edit]

The BDNF protein is encoded by a gene that is also called BDNF, found in humans on chromosome 11.[7][8] Structurally, BDNF transcription is controlled by eight different promoters, each leading to different transcripts containing one of eight untranslated 5' exons (I to VIII) spliced to the 3' encoding exon. Promoter IV activity, leading to the translation of exon IV-containing mRNA, is strongly stimulated by calcium and is primarily under the control of a Cre regulatory component, suggesting a putative role for the transcription factor CREB and the source of BDNF's activity-dependent effects .[34] There are multiple mechanisms through neuronal activity that can increase BDNF exon IV specific expression.[34] Stimulus-mediated neuronal excitation can lead to NMDA receptor activation, triggering a calcium influx. Through a protein signaling cascade requiring Erk, CaM KII/IV, PI3K, and PLC, NMDA receptor activation is capable of triggering BDNF exon IV transcription. BDNF exon IV expression also seems capable of further stimulating its own expression through TrkB activation. BDNF is released from the post-synaptic membrane in an activity-dependent manner, allowing it to act on local TrkB receptors and mediate effects that can lead to signaling cascades also involving Erk and CaM KII/IV.[34][35] Both of these pathways probably involve calcium-mediated phosphorylation of CREB at Ser133, thus allowing it to interact with BDNF's Cre regulatory domain and upregulate transcription.[36] However, NMDA-mediated receptor signaling is probably necessary to trigger the upregulation of BDNF exon IV expression because normally CREB interaction with CRE and the subsequent translation of the BDNF transcript is blocked by of the basic helix–loop–helix transcription factor protein 2 (BHLHB2).[37] NMDA receptor activation triggers the release of the regulatory inhibitor, allowing for BDNF exon IV upregulation to take place in response to the activity-initiated calcium influx.[37] Activation of dopamine receptor D5 also promotes expression of BDNF in prefrontal cortex neurons.[38]

Common SNPs in BDNF gene

[edit]

BDNF has several known single nucleotide polymorphisms (SNP), including, but not limited to, rs6265, C270T, rs7103411, rs2030324, rs2203877, rs2049045 and rs7124442. As of 2008, rs6265 is the most investigated SNP of the BDNF gene [39][40]

Val66Met

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A common SNP in the BDNF gene is rs6265.[41] This point mutation in the coding sequence, a guanine to adenine switch at position 196, results in an amino acid switch: valine to methionine exchange at codon 66, Val66Met, which is in the prodomain of BDNF.[41][40] Val66Met is unique to humans.[41][40]

The mutation interferes with normal translation and intracellular trafficking of BDNF mRNA, as it destabilizes the mRNA and renders it prone to degradation.[41] The proteins resulting from mRNA that does get translated, are not trafficked and secreted normally, as the amino acid change occurs on the portion of the prodomain where sortilin binds; and sortilin is essential for normal trafficking.[41][40][42]

The Val66Met mutation results in a reduction of hippocampal tissue and has since been reported in a high number of individuals with learning and memory disorders,[40] anxiety disorders,[43] major depression,[44] and neurodegenerative diseases such as Alzheimer's and Parkinson's.[45]

A meta-analysis indicates that the BDNF Val66Met variant is not associated with serum BDNF.[46]

Role in synaptic transmission

[edit]

Glutamatergic signaling

[edit]

Glutamate is the brain's major excitatory neurotransmitter and its release can trigger the depolarization of postsynaptic neurons. AMPA and NMDA receptors are two ionotropic glutamate receptors involved in glutamatergic neurotransmission and essential to learning and memory via long-term potentiation. While AMPA receptor activation leads to depolarization via sodium influx, NMDA receptor activation by rapid successive firing allows calcium influx in addition to sodium. The calcium influx triggered through NMDA receptors can lead to expression of BDNF, as well as other genes thought to be involved in LTP, dendritogenesis, and synaptic stabilization.

NMDA receptor activity

[edit]

NMDA receptor activation is essential to producing the activity-dependent molecular changes involved in the formation of new memories. Following exposure to an enriched environment, BDNF and NR1 phosphorylation levels are upregulated simultaneously, probably because BDNF is capable of phosphorylating NR1 subunits, in addition to its many other effects.[47][48] One of the primary ways BDNF can modulate NMDA receptor activity is through phosphorylation and activation of the NMDA receptor one subunit, particularly at the PKC Ser-897 site.[47] The mechanism underlying this activity is dependent upon both ERK and PKC signaling pathways, each acting individually, and all NR1 phosphorylation activity is lost if the TrKB receptor is blocked.[47] PI3 kinase and Akt are also essential in BDNF-induced potentiation of NMDA receptor function and inhibition of either molecule eliminated receptor BDNF can also increase NMDA receptor activity through phosphorylation of the NR2B subunit. BDNF signaling leads to the autophosphorylation of the intracellular domain of the TrkB receptor (ICD-TrkB). Upon autophosphorylation, Fyn associates with the pICD-TrkB through its Src homology domain 2 (SH2) and is phosphorylated at its Y416 site.[49][50] Once activated, Fyn can bind to NR2B through its SH2 domain and mediate phosphorylation of its Tyr-1472 site.[51] Similar studies have suggested Fyn is also capable of activating NR2A although this was not found in the hippocampus.[52][53] Thus, BDNF can increase NMDA receptor activity through Fyn activation. This has been shown to be important for processes such as spatial memory in the hippocampus, demonstrating the therapeutic and functional relevance of BDNF-mediated NMDA receptor activation.[52]

Synapse stability

[edit]

In addition to mediating transient effects on NMDAR activation to promote memory-related molecular changes, BDNF should also initiate more stable effects that could be maintained in its absence and not depend on its expression for long term synaptic support.[54] It was previously mentioned that AMPA receptor expression is essential to learning and memory formation, as these are the components of the synapse that will communicate regularly and maintain the synapse structure and function long after the initial activation of NMDA channels. BDNF is capable of increasing the mRNA expression of GluR1 and GluR2 through its interaction with the TrkB receptor and promoting the synaptic localization of GluR1 via PKC- and CaMKII-mediated Ser-831 phosphorylation.[55] It also appears that BDNF is able to influence Gl1 activity through its effects on NMDA receptor activity.[56] BDNF significantly enhanced the activation of GluR1 through phosphorylation of tyrosine830, an effect that was abolished in either the presence of a specific NR2B antagonist or a trk receptor tyrosine kinase inhibitor.[56] Thus, it appears BDNF can upregulate the expression and synaptic localization of AMPA receptors, as well as enhance their activity through its postsynaptic interactions with the NR2B subunit. This suggests BDNF is not only capable of initiating synapse formation through its effects on NMDA receptor activity, but it can also support the regular every-day signaling necessary for stable memory function.

GABAergic signaling

[edit]

One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing GABAergic signaling activities.[57] While glutamate is the brain's major excitatory neurotransmitter and phosphorylation normally activates receptors, GABA is the brain's primary inhibitory neurotransmitter and phosphorylation of GABAA receptors tend to reduce their activity.[clarification needed] Blockading BDNF signaling with a tyrosine kinase inhibitor or a PKC inhibitor in wild type mice produced significant reductions in spontaneous action potential frequencies that were mediated by an increase in the amplitude of GABAergic inhibitory postsynaptic currents (IPSC).[57] Similar effects could be obtained in BDNF knockout mice, but these effects were reversed by local application of BDNF.[57] This suggests BDNF increases excitatory synaptic signaling partly through the post-synaptic suppression of GABAergic signaling by activating PKC through its association with TrkB.[57] Once activated, PKC can reduce the amplitude of IPSCs through to GABAA receptor phosphorylation and inhibition.[57] In support of this putative mechanism, activation of PKCε leads to phosphorylation of N-ethylmaleimide-sensitive factor (NSF) at serine 460 and threonine 461, increasing its ATPase activity which downregulates GABAA receptor surface expression and subsequently attenuates inhibitory currents.[58]

Synaptogenesis

[edit]

BDNF also enhances synaptogenesis. Synaptogenesis is dependent upon the assembly of new synapses and the disassembly of old synapses by β-adducin.[59] Adducins are membrane-skeletal proteins that cap the growing ends of actin filaments and promote their association with spectrin, another cytoskeletal protein, to create stable and integrated cytoskeletal networks.[60] Actins have a variety of roles in synaptic functioning. In pre-synaptic neurons, actins are involved in synaptic vesicle recruitment and vesicle recovery following neurotransmitter release.[61] In post-synaptic neurons they can influence dendritic spine formation and retraction as well as AMPA receptor insertion and removal.[61] At their C-terminus, adducins possess a myristoylated alanine-rich C kinase substrate (MARCKS) domain which regulates their capping activity.[60] BDNF can reduce capping activities by upregulating PKC, which can bind to the adducing MRCKS domain, inhibit capping activity, and promote synaptogenesis through dendritic spine growth and disassembly and other activities.[59][61]

Dendritogenesis

[edit]

Local interaction of BDNF with the TrkB receptor on a single dendritic segment is able to stimulate an increase in PSD-95 trafficking to other separate dendrites as well as to the synapses of locally stimulated neurons.[62] PSD-95 localizes the actin-remodeling GTPases, Rac and Rho, to synapses through the binding of its PDZ domain to kalirin, increasing the number and size of spines.[63] Thus, BDNF-induced trafficking of PSD-95 to dendrites stimulates actin remodeling and causes dendritic growth in response to BDNF.

Neurogenesis

[edit]

Laboratory studies indicate that BDNF may play a role in neurogenesis. BDNF can promote protective pathways and inhibit damaging pathways in the NSCs and NPCs that contribute to the brain's neurogenic response by enhancing cell survival. This becomes especially evident following suppression of TrkB activity.[32] TrkB inhibition results in a 2–3 fold increase in cortical precursors displaying EGFP-positive condensed apoptotic nuclei and a 2–4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[32] BDNF can also promote NSC and NPC proliferation through Akt activation and PTEN inactivation.[64] Some studies suggest that BDNF may promote neuronal differentiation.[32][65]

Research

[edit]

Preliminary research has focused on the possible links between BDNF and clinical conditions, such as depression,[66] schizophrenia,[67] and Alzheimer's disease.[68]

Schizophrenia

[edit]
See also: Epigenetics of schizophrenia § Methylation of BDNF

Preliminary studies have assessed a possible relationship between schizophrenia and BDNF.[69] It has been shown that BDNF mRNA levels are decreased in cortical layers IV and V of the dorsolateral prefrontal cortex of schizophrenic patients, an area associated with working memory.[70]

Depression

[edit]
See also: Epigenetics of depression § Brain-derived neurotrophic factor

The neurotrophic hypothesis of depression states that depression is associated with a decrease in the levels of BDNF.[66]

Epilepsy

[edit]

Levels of both BDNF mRNA and BDNF protein are known to be up-regulated in epilepsy.[71]

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000176697 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048482 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Anti-Brain Derived Neurotrophic Factor Antibody, pro". sigmaaldrich.com. Retrieved 20 August 2023.
  6. ^ Binder DK, Scharfman HE (September 2004). "Brain-derived neurotrophic factor". Growth Factors. 22 (3): 123–31. doi:10.1080/08977190410001723308. PMC 2504526. PMID 15518235. found in the [clarification needed] and the periphery.
  7. ^ a b Jones KR, Reichardt LF (October 1990). "Molecular cloning of a human gene that is a member of the nerve growth factor family". Proceedings of the National Academy of Sciences of the United States of America. 87 (20): 8060–64. Bibcode:1990PNAS...87.8060J. doi:10.1073/pnas.87.20.8060. PMC 54892. PMID 2236018.
  8. ^ a b Maisonpierre PC, Le Beau MM, Espinosa R, Ip NY, Belluscio L, de la Monte SM, et al. (July 1991). "Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations". Genomics. 10 (3): 558–68. doi:10.1016/0888-7543(91)90436-I. PMID 1889806.
  9. ^ Kowiański P, Lietzau G, Czuba E, Waśkow M, Steliga A, Moryś J (April 2018). "BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity". Cellular and Molecular Neurobiology. 38 (3): 579–593. doi:10.1007/s10571-017-0510-4. PMC 5835061. PMID 28623429.
  10. ^ a b c Squinto SP, Stitt TN, Aldrich TH, Valenzuela DM, DiStefano PS, Yancopoulos GD (May 1991). "trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor". Cell. 65 (5): 885–893. doi:10.1016/0092-8674(91)90395-f. PMID 1710174. S2CID 28853455.
  11. ^ a b c Glass DJ, Nye SH, Hantzopoulos P, Macchi MJ, Squinto SP, Goldfarb M, et al. (July 1991). "TrkB mediates BDNF/NT-3-dependent survival and proliferation in fibroblasts lacking the low affinity NGF receptor". Cell. 66 (2): 405–413. doi:10.1016/0092-8674(91)90629-d. PMID 1649703. S2CID 43626580.
  12. ^ Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, et al. (March 1995). "A BDNF autocrine loop in adult sensory neurons prevents cell death". Nature. 374 (6521): 450–53. Bibcode:1995Natur.374..450A. doi:10.1038/374450a0. PMID 7700353. S2CID 4316241.
  13. ^ Huang EJ, Reichardt LF (2001). "Neurotrophins: roles in neuronal development and function". Annual Review of Neuroscience. 24: 677–736. doi:10.1146/annurev.neuro.24.1.677. PMC 2758233. PMID 11520916.
  14. ^ Yamada K, Nabeshima T (April 2003). "Brain-derived neurotrophic factor/TrkB signaling in memory processes". Journal of Pharmacological Sciences. 91 (4): 267–70. doi:10.1254/jphs.91.267. PMID 12719654.
  15. ^ Mandel AL, Ozdener H, Utermohlen V (July 2009). "Identification of pro- and mature brain-derived neurotrophic factor in human saliva". Archives of Oral Biology. 54 (7): 689–95. doi:10.1016/j.archoralbio.2009.04.005. PMC 2716651. PMID 19467646.
  16. ^ a b Delezie J, Handschin C (2018). "Endocrine Crosstalk Between Skeletal Muscle and the Brain". Frontiers in Neurology. 9: 698. doi:10.3389/fneur.2018.00698. PMC 6117390. PMID 30197620.
  17. ^ Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, et al. (February 2008). "BDNF is essential to promote persistence of long-term memory storage". Proceedings of the National Academy of Sciences of the United States of America. 105 (7): 2711–16. Bibcode:2008PNAS..105.2711B. doi:10.1073/pnas.0711863105. PMC 2268201. PMID 18263738.
  18. ^ Zigova T, Pencea V, Wiegand SJ, Luskin MB (July 1998). "Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb". Molecular and Cellular Neurosciences. 11 (4): 234–45. doi:10.1006/mcne.1998.0684. PMID 9675054. S2CID 35630924.
  19. ^ Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA (September 2001). "Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain". The Journal of Neuroscience. 21 (17): 6718–31. doi:10.1523/JNEUROSCI.21-17-06718.2001. PMC 6763117. PMID 11517261.
  20. ^ Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (September 2001). "Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus". The Journal of Neuroscience. 21 (17): 6706–17. doi:10.1523/JNEUROSCI.21-17-06706.2001. PMC 6763082. PMID 11517260.
  21. ^ Ernfors P, Kucera J, Lee KF, Loring J, Jaenisch R (October 1995). "Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice". The International Journal of Developmental Biology. 39 (5): 799–807. PMID 8645564.
  22. ^ MGI database: phenotypes for BDNF homozygous null mice. http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537&int:_Set_key=847156
  23. ^ Szuhany KL, Bugatti M, Otto MW (January 2015). "A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor". Journal of Psychiatric Research. 60: 56–64. doi:10.1016/j.jpsychires.2014.10.003. PMC 4314337. PMID 25455510.
  24. ^ Denham J, Marques FZ, O'Brien BJ, Charchar FJ (February 2014). "Exercise: putting action into our epigenome". Sports Medicine. 44 (2): 189–209. doi:10.1007/s40279-013-0114-1. PMID 24163284. S2CID 30210091.
  25. ^ Phillips C, Baktir MA, Srivatsan M, Salehi A (2014). "Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling". Frontiers in Cellular Neuroscience. 8: 170. doi:10.3389/fncel.2014.00170. PMC 4064707. PMID 24999318.
  26. ^ Heinonen I, Kalliokoski KK, Hannukainen JC, Duncker DJ, Nuutila P, Knuuti J (November 2014). "Organ-specific physiological responses to acute physical exercise and long-term training in humans". Physiology. 29 (6): 421–36. doi:10.1152/physiol.00067.2013. PMID 25362636.
  27. ^ Fu L, Doreswamy V, Prakash R (August 2014). "The biochemical pathways of central nervous system neural degeneration in niacin deficiency". Neural Regeneration Research. 9 (16): 1509–13. doi:10.4103/1673-5374.139475. PMC 4192966. PMID 25317166.
  28. ^ Patapoutian A, Reichardt LF (June 2001). "Trk receptors: mediators of neurotrophin action". Current Opinion in Neurobiology. 11 (3): 272–80. doi:10.1016/S0959-4388(00)00208-7. PMID 11399424. S2CID 8000523.
  29. ^ Fernandes CC, Pinto-Duarte A, Ribeiro JA, Sebastião AM (May 2008). "Postsynaptic action of brain-derived neurotrophic factor attenuates alpha7 nicotinic acetylcholine receptor-mediated responses in hippocampal interneurons". The Journal of Neuroscience. 28 (21): 5611–18. doi:10.1523/JNEUROSCI.5378-07.2008. PMC 6670615. PMID 18495895.
  30. ^ Fatemi, S. Hossein (2005). Reelin glycoprotein: Structure, biology and roles in health and disease. Vol. 10. Berlin: Springer. pp. 251–7. doi:10.1038/sj.mp.4001613. ISBN 978-0-387-76760-4. PMID 15583703. S2CID 21206951. {{cite book}}: |journal= ignored (help); see the chapter "A Tale of Two Genes: Reelin and BDNF"; pp. 237–45
  31. ^ Ringstedt T, Linnarsson S, Wagner J, Lendahl U, Kokaia Z, Arenas E, et al. (August 1998). "BDNF regulates reelin expression and Cajal-Retzius cell development in the cerebral cortex". Neuron. 21 (2): 305–15. doi:10.1016/S0896-6273(00)80540-1. PMID 9728912. S2CID 13983709.
  32. ^ a b c d e Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, Miller FD (December 2007). "Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development". Development. 134 (24): 4369–80. doi:10.1242/dev.008227. PMID 18003743.
  33. ^ Michaelsen K, Zagrebelsky M, Berndt-Huch J, Polack M, Buschler A, Sendtner M, et al. (December 2010). "Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons". The European Journal of Neuroscience. 32 (11): 1854–65. doi:10.1111/j.1460-9568.2010.07460.x. PMID 20955473. S2CID 23496332.
  34. ^ a b c Zheng F, Wang H (2009). "NMDA-mediated and self-induced bdnf exon IV transcriptions are differentially regulated in cultured cortical neurons". Neurochemistry International. 54 (5–6): 385–92. doi:10.1016/j.neuint.2009.01.006. PMC 2722960. PMID 19418634.
  35. ^ Kuzumaki N, Ikegami D, Tamura R, Hareyama N, Imai S, Narita M, et al. (February 2011). "Hippocampal epigenetic modification at the brain-derived neurotrophic factor gene induced by an enriched environment". Hippocampus. 21 (2): 127–32. doi:10.1002/hipo.20775. PMID 20232397. S2CID 205912003.
  36. ^ Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (April 1998). "Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism". Neuron. 20 (4): 709–26. doi:10.1016/s0896-6273(00)81010-7. PMID 9581763. S2CID 770523.
  37. ^ a b Jiang X, Tian F, Du Y, Copeland NG, Jenkins NA, Tessarollo L, et al. (January 2008). "BHLHB2 controls Bdnf promoter 4 activity and neuronal excitability". The Journal of Neuroscience. 28 (5): 1118–30. doi:10.1523/JNEUROSCI.2262-07.2008. PMC 6671398. PMID 18234890.
  38. ^ Perreault ML, Jones-Tabah J, O'Dowd BF, George SR (March 2013). "A physiological role for the dopamine D5 receptor as a regulator of BDNF and Akt signalling in rodent prefrontal cortex". The International Journal of Neuropsychopharmacology. 16 (2): 477–83. doi:10.1017/S1461145712000685. PMC 3802523. PMID 22827965.
  39. ^ Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. (January 2003). "The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function". Cell. 112 (2): 257–69. doi:10.1016/S0092-8674(03)00035-7. PMID 12553913. S2CID 12748901.
  40. ^ a b c d e Bath KG, Lee FS (March 2006). "Variant BDNF (Val66Met) impact on brain structure and function". Cognitive, Affective, & Behavioral Neuroscience. 6 (1): 79–85. doi:10.3758/CABN.6.1.79. PMID 16869232.
  41. ^ a b c d e Baj G, Carlino D, Gardossi L, Tongiorgi E (October 2013). "Toward a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: a model of impaired dendritic mRNA trafficking". Frontiers in Neuroscience. 7: 188. doi:10.3389/fnins.2013.00188. PMC 3812868. PMID 24198753.
  42. ^ Cunha C, Brambilla R, Thomas KL (1 January 2010). "A simple role for BDNF in learning and memory?". Frontiers in Molecular Neuroscience. 3: 1. doi:10.3389/neuro.02.001.2010. PMC 2821174. PMID 20162032.
  43. ^ Dincheva I, Lynch NB, Lee FS (October 2016). "The Role of BDNF in the Development of Fear Learning". Depression and Anxiety. 33 (10): 907–916. doi:10.1002/da.22497. PMC 5089164. PMID 27699937.
  44. ^ Youssef MM, Underwood MD, Huang YY, Hsiung SC, Liu Y, Simpson NR, et al. (June 2018). "Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide". The International Journal of Neuropsychopharmacology. 21 (6): 528–538. doi:10.1093/ijnp/pyy008. PMC 6007393. PMID 29432620.
  45. ^ Lu B, Nagappan G, Guan X, Nathan PJ, Wren P (June 2013). "BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases". Nature Reviews. Neuroscience. 14 (6): 401–16. doi:10.1038/nrn3505. PMID 23674053. S2CID 2065483.
  46. ^ Terracciano A, Piras MG, Lobina M, Mulas A, Meirelles O, Sutin AR, et al. (December 2013). "Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association study". The World Journal of Biological Psychiatry. 14 (8): 583–89. doi:10.3109/15622975.2011.616533. PMC 3288597. PMID 22047184.
  47. ^ a b c Slack SE, Pezet S, McMahon SB, Thompson SW, Malcangio M (October 2004). "Brain-derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord". The European Journal of Neuroscience. 20 (7): 1769–78. doi:10.1111/j.1460-9568.2004.03656.x. PMID 15379998. S2CID 23108942.
  48. ^ Xu X, Ye L, Ruan Q (March 2009). "Environmental enrichment induces synaptic structural modification after transient focal cerebral ischemia in rats". Experimental Biology and Medicine. 234 (3): 296–305. doi:10.3181/0804-RM-128. PMID 19244205. S2CID 39825785.
  49. ^ Namekata K, Harada C, Taya C, Guo X, Kimura H, Parada LF, et al. (April 2010). "Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex". Proceedings of the National Academy of Sciences of the United States of America. 107 (16): 7586–91. Bibcode:2010PNAS..107.7586N. doi:10.1073/pnas.0914514107. PMC 2867726. PMID 20368433.
  50. ^ Iwasaki Y, Gay B, Wada K, Koizumi S (July 1998). "Association of the Src family tyrosine kinase Fyn with TrkB". Journal of Neurochemistry. 71 (1): 106–11. doi:10.1046/j.1471-4159.1998.71010106.x. PMID 9648856. S2CID 9012343.
  51. ^ Nakazawa T, Komai S, Tezuka T, Hisatsune C, Umemori H, Semba K, et al. (January 2001). "Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor". The Journal of Biological Chemistry. 276 (1): 693–99. doi:10.1074/jbc.M008085200. PMID 11024032.
  52. ^ a b Mizuno M, Yamada K, He J, Nakajima A, Nabeshima T (2003). "Involvement of BDNF receptor TrkB in spatial memory formation". Learning & Memory. 10 (2): 108–15. doi:10.1101/lm.56003. PMC 196664. PMID 12663749.
  53. ^ Tezuka T, Umemori H, Akiyama T, Nakanishi S, Yamamoto T (January 1999). "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proceedings of the National Academy of Sciences of the United States of America. 96 (2): 435–40. Bibcode:1999PNAS...96..435T. doi:10.1073/pnas.96.2.435. PMC 15154. PMID 9892651.
  54. ^ Briones TL, Suh E, Jozsa L, Hattar H, Chai J, Wadowska M (February 2004). "Behaviorally-induced ultrastructural plasticity in the hippocampal region after cerebral ischemia". Brain Research. 997 (2): 137–46. doi:10.1016/j.brainres.2003.10.030. PMID 14706865. S2CID 34763792.
  55. ^ Caldeira MV, Melo CV, Pereira DB, Carvalho R, Correia SS, Backos DS, et al. (April 2007). "Brain-derived neurotrophic factor regulates the expression and synaptic delivery of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits in hippocampal neurons". The Journal of Biological Chemistry. 282 (17): 12619–28. doi:10.1074/jbc.M700607200. PMID 17337442.
  56. ^ a b Wu K, Len GW, McAuliffe G, Ma C, Tai JP, Xu F, et al. (November 2004). "Brain-derived neurotrophic factor acutely enhances tyrosine phosphorylation of the AMPA receptor subunit GluR1 via NMDA receptor-dependent mechanisms". Brain Research. Molecular Brain Research. 130 (1–2): 178–86. doi:10.1016/j.molbrainres.2004.07.019. PMID 15519688.
  57. ^ a b c d e Henneberger C, Jüttner R, Rothe T, Grantyn R (August 2002). "Postsynaptic action of BDNF on GABAergic synaptic transmission in the superficial layers of the mouse superior colliculus". Journal of Neurophysiology. 88 (2): 595–603. doi:10.1152/jn.2002.88.2.595. PMID 12163512. S2CID 9287511.
  58. ^ Chou WH, Wang D, McMahon T, Qi ZH, Song M, Zhang C, et al. (October 2010). "GABAA receptor trafficking is regulated by protein kinase C(epsilon) and the N-ethylmaleimide-sensitive factor". The Journal of Neuroscience. 30 (42): 13955–65. doi:10.1523/JNEUROSCI.0270-10.2010. PMC 2994917. PMID 20962217.
  59. ^ a b Bednarek E, Caroni P (March 2011). "β-Adducin is required for stable assembly of new synapses and improved memory upon environmental enrichment". Neuron. 69 (6): 1132–46. doi:10.1016/j.neuron.2011.02.034. PMID 21435558. S2CID 15373477.
  60. ^ a b Matsuoka Y, Li X, Bennett V (June 2000). "Adducin: structure, function and regulation". Cellular and Molecular Life Sciences. 57 (6): 884–95. doi:10.1007/pl00000731. PMC 11146971. PMID 10950304. S2CID 29317393.
  61. ^ a b c Stevens RJ, Littleton JT (May 2011). "Synaptic growth: dancing with adducin". Current Biology. 21 (10): R402–5. Bibcode:2011CBio...21.R402S. doi:10.1016/j.cub.2011.04.020. hdl:1721.1/92025. PMID 21601803. S2CID 3182599.
  62. ^ Yoshii A, Constantine-Paton M (June 2007). "BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation". Nature Neuroscience. 10 (6): 702–11. doi:10.1038/nn1903. PMID 17515902. S2CID 6486137.
  63. ^ Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V, et al. (January 2001). "The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis". Neuron. 29 (1): 229–42. doi:10.1016/s0896-6273(01)00193-3. PMID 11182094. S2CID 7014018.
  64. ^ Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM (July 1999). "PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway". The Journal of Biological Chemistry. 274 (29): 20693–703. doi:10.1074/jbc.274.29.20693. PMID 10400703.
  65. ^ Bath KG, Akins MR, Lee FS (September 2012). "BDNF control of adult SVZ neurogenesis". Developmental Psychobiology. 54 (6): 578–89. doi:10.1002/dev.20546. PMC 3139728. PMID 21432850.
  66. ^ a b Cavaleri D, Moretti F, Bartoccetti A, Mauro S, Crocamo C, Carrà G, et al. (April 2023). "The role of BDNF in major depressive disorder, related clinical features, and antidepressant treatment: Insight from meta-analyses". Review. Neuroscience and Biobehavioral Reviews. 149: 105159. doi:10.1016/j.neubiorev.2023.105159. hdl:10281/412775. PMID 37019247. S2CID 257915698.
  67. ^ Xiu MH, Hui L, Dang YF, Hou TD, Zhang CX, Zheng YL, et al. (November 2009). "Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 33 (8): 1508–12. doi:10.1016/j.pnpbp.2009.08.011. PMID 19720106. S2CID 43300334.
  68. ^ Zuccato C, Cattaneo E (June 2009). "Brain-derived neurotrophic factor in neurodegenerative diseases". Nature Reviews. Neurology. 5 (6): 311–22. doi:10.1038/nrneurol.2009.54. PMID 19498435. S2CID 30782827.
  69. ^ Xiong P, Zeng Y, Wu Q, Han Huang DX, Zainal H, Xu X, et al. (August 2014). "Combining serum protein concentrations to diagnose schizophrenia: a preliminary exploration". The Journal of Clinical Psychiatry. 75 (8): e794–801. doi:10.4088/JCP.13m08772. PMID 25191916.
  70. ^ Ray MT, Shannon Weickert C, Webster MJ (May 2014). "Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders". Translational Psychiatry. 4 (5): e389. doi:10.1038/tp.2014.26. PMC 4035720. PMID 24802307.
  71. ^ Gall C, Lauterborn J, Bundman M, Murray K, Isackson P (1991). "Seizures and the regulation of neurotrophic factor and neuropeptide gene expression in brain". Epilepsy Research. Supplement. 4: 225–45. PMID 1815605.
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