Open main menu

Wikipedia β

Brain-derived neurotrophic factor

  (Redirected from BDNF)

Brain-derived neurotrophic factor, also known as BDNF, is a protein[5] that, in humans, is encoded by the BDNF gene.[6][7] BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical Nerve Growth Factor. Neurotrophic factors are found in the brain and the periphery.

BDNF
Brain-derived neurotrophic factor - PDB id 1BND.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases BDNF, brain-derived neurotrophic factor, ANON2, BULN2, Brain-derived neurotrophic factor, brain derived neurotrophic factor
External IDs OMIM: 113505 MGI: 88145 HomoloGene: 7245 GeneCards: BDNF
Gene location (Human)
Chromosome 11 (human)
Chr. Chromosome 11 (human)[1]
Chromosome 11 (human)
Genomic location for BDNF
Genomic location for BDNF
Band 11p14.1 Start 27,654,893 bp[1]
End 27,722,058 bp[1]
RNA expression pattern
PBB GE BDNF 206382 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC) Chr 11: 27.65 – 27.72 Mb Chr 11: 109.67 – 109.73 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Contents

FunctionEdit

BDNF acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses.[8][9] In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking.[10] It is also expressed in the retina, motor neurons, the kidneys, saliva, and the prostate.[11]

BDNF itself is important for long-term memory.[12] 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.[13][14][15] Mice born without the ability to make BDNF suffer 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.[16] 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 the disruption of this binding has been proposed to cause the loss of sorting of 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.[17]

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.[18][19][20][21] Niacin appears to upregulate BDNF and tropomyosin receptor kinase B (TrkB) expression as well.[22]

Mechanism of actionEdit

BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkB (pronounced "Track B") and the LNGFR (for low-affinity nerve growth factor receptor, also known as p75).[23] It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor.[24] BDNF has also been shown to interact with the reelin signaling chain.[25] The expression of reelin by Cajal-Retzius cells goes down during development under the influence of BDNF.[26] The latter also decreases reelin expression in neuronal culture.

TrkBEdit

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, a widely expressed activity-dependent neurotic factor that regulates plasticity and is unregulated 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]

LNGFREdit

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.[27] When the p75 receptor is activated, it leads to activation of NFkB receptor.[27] 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.[28]

ExpressionEdit

The BDNF protein is encoded by a gene that is also called BDNF, found in humans on chromosome 11.[6][7] Structurally, BDNF transcription is controlled by 8 different promoters, each leading to different transcripts containing one of 8 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 .[29] There are multiple mechanisms through neuronal activity can increase BDNF exon IV specific expression.[29] 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 leading to signaling cascades also involving Erk and CaM KII/IV.[29][30] 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.[31] 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).[32] 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.[32] Activation of Dopamine receptor D5 also promotes expression of BDNF in prefrontal cortex neurons.[33]

Common SNPs in BDNF geneEdit

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 [34][35]

Val66MetEdit

A common SNP in the BDNF gene is rs6265.[36] 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.[36][35] Val66Met is unique to humans.[36][35]

The mutation interferes with normal translation and intracellular trafficking of BDNF mRNA, as it destabilizes the mRNA and renders it prone to degradation.[36] 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.[36][35][37]

The Val66Met mutation results in a reduction of hippocampal tissue and has since been reported in a high number of individuals suffering from learning and memory disorders,[35] anxiety disorders,[38] and neurodegenerative diseases such as Alzheimer’s and Parkinson’s.[39]

A meta-analysis indicates that the BDNF Val66Met variant is not associated with serum BDNF.[40]

Role in synaptic transmissionEdit

Glutamatergic signalingEdit

Glutamate is the brain’s major excitatory neurotransmitter and its release can trigger the depolarization of postsynaptic neurons. AMPA and NMDA receptors are two major ionotropic receptors that are especially suspected of being involved in learning and memory. While AMPA receptor activation leads to depolarization via sodium influx, NMDA receptor activation leads to depolarization via calcium and sodium influx. The calcium influx triggered through NMDA receptors can lead to the activity-dependent expression of many different genes, proteins, and receptors that are thought to be involved in processes involving learning, memory, neurogenesis, and environmental responses. The activity-dependent synaptic responses also lead to rapid insertion of AMPA receptors into the postsynaptic membrane, which will act to maintain ongoing glutamatergic transmission as sustained calcium influx could result in excitotoxicity

NMDA receptor activityEdit

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.[41][42] 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.[41] 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.[41] PI3 kinase and Akt are also essential in BDNF-induced potentiation of NMDA receptor function and inhibition of either molecule completely eliminated receptor activity.[42] 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.[43][44] Once activated, Fyn can bind to NR2B through its SH2 domain and mediate phosphorylation of its Tyr-1472 site.[45] Similar studies have suggested Fyn is also capable of activating NR2A although this was not found in the hippocampus.[46][47] 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.[46]

Synapse stabilityEdit

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.[48] 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.[49] It also appears that BDNF is able to influence Gl1 activity through its effects on NMDA receptor activity.[50] 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.[50] 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 signalingEdit

One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing GABAergic signaling activities.[51] 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. 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).[51] Similar effects could be obtained in BDNF knockout mice, but these effects were reversed by local application of BDNF.[51] This suggests BDNF increases excitatory synaptic signaling partly through the post-synaptic suppression of GABAergic of signaling by activating PKC through its association with TrkB.[51] Once activated, PKC can reduce the amplitude of IPSCs through to GABAA receptor phosphorylation and inhibition.[51] 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.[52]

SynaptogenesisEdit

BDNF also enhances synaptogenesis. Synaptogenesis is dependent upon the assembly of new synapses and the disassembly of old synapses by β-adducin.[53] 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.[54] 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.[55] In post-synaptic neurons they can influence dendritic spine formation and retraction as well as AMPA receptor insertion and removal.[55] At their C-terminus, adducins possess a myristoylated alanine-rich C kinase substrate (MARCKS) domain which regulates their capping activity.[54] BDNF can reduce capping activities by upregulating PKC, which can bind to the adducing MRCKS domain, inhibit capping activity, and promote synatogenesis through dendritic spine growth and disassembly and other activities.[53][55]

DendritogenesisEdit

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.[56] 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.[57] Thus, BDNF-induced trafficking of PSD-95 to dendrites stimulates actin remodeling and causes dendritic growth in response to BDNF.

NeurogenesisEdit

BDNF plays a significant 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.[27] 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.[27] BDNF can also promote NSC and NPC proliferation through Akt activation and PTEN inactivation.[58] There have been many in vivo studies demonstrating BDNF is a strong promoter of neuronal differentiation.[27][59] Infusion of BDNF into the lateral ventricles doubled the population of newborn neurons in the adult rat olfactory bulb and viral overexpression of BDNF can similarly enhance SVZ neurogenesis.[13][14][59] BDNF might also play a role in NSC/NPC migration. By stabilizing p35 (CDK5R1), in utero electroporation studies revealed BDNF was able to promote cortical radial migration by about 2.3-fold in embryonic rats, an effect which was dependent on the activity of the trkB receptor.[60]

Cognitive functionEdit

Enriched housing provides the opportunity for exercise and exposure to multimodal stimuli. The increased visual, physical, and cognitive stimulation all translates into more neuronal activity and synaptic communication, which can produce structural or molecular activity-dependent alterations.[61][62] Sensory inputs from environmental stimuli are initially processed by the cortex before being transmitted to the hippocampus along an afferent pathway, suggesting the activity-mediated effects of enrichment can be far-reaching within the brain.[62] BDNF expression is significantly enhanced by environmental enrichment and appears to be the primary source of environmental enrichments ability to enhance cognitive processes. Environmental enrichment enhances synaptogenesis, dendridogenesis, and neurogenesis, leading to improved performance on various learning and memory tasks. BDNF mediates more pathways involved in these enrichment-induced processes than any other molecule and is strongly regulated by calcium activity making it incredibly sensitive to neuronal activity.

Disease linkageEdit

Various studies have shown possible links between BDNF and conditions, such as depression,[63][64] schizophrenia,[65] obsessive-compulsive disorder,[66] Alzheimer's disease,[67] Huntington's disease,[68] Rett syndrome,[69] and dementia,[70] as well as anorexia nervosa[71] and bulimia nervosa.[72] Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when expressed in the ventral tegmental area in rats.[73]

As of 2002 clinical trials in which BDNF was delivered into the central nervous system (CNS) of humans with various neurodegenerative disease had all failed.[74]

SchizophreniaEdit

A plethora of recent evidence suggests the linkage between schizophrenia and BDNF.[75] Given that BDNF is critical for the survival of central nervous system (CNS) and peripheral nervous system (PNS) neurons and synaptogenesis during and even after development, BDNF alterations may play a role in the pathogenesis of schizophrenia. BDNF has been found within many areas of the brain and plays an important role is supporting the formation of memories.[12] 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 that is known to be involved with working memory.[76] Since schizophrenic patients often suffer from impairments in working memory, and BDNF mRNA levels have been shown to be decreased in the DLPFC of schizophrenic patients, it is highly likely that BDNF plays some role in the etiology of this neurodevelopmental disorder of the CNS.

DepressionEdit

Exposure to stress and the stress hormone corticosterone has been shown to decrease the expression of BDNF in rats, and, if exposure is persistent, this leads to an eventual atrophy of the hippocampus. Atrophy of the hippocampus and other limbic structures has been shown to take place in humans suffering from chronic depression.[77] In addition, rats bred to be heterozygous for BDNF, therefore reducing its expression, have been observed to exhibit similar hippocampal atrophy. This suggests that an etiological link between the development of depression and BDNF exists. Supporting this, the excitatory neurotransmitter glutamate, voluntary exercise,[78] caloric restriction, intellectual stimulation, curcumin[79] and various treatments for depression (such as antidepressants[80] and electroconvulsive therapy[81]) increase expression of BDNF in the brain. In the case of some treatments such as drugs[82] and electroconvulsive therapy[83] this has been shown to protect against or reverse this atrophy.[82]

Alzheimer's diseaseEdit

Post mortem analysis has shown lowered levels of BDNF in the brain tissues of people with Alzheimer's disease, although the nature of the connection remains unclear. Studies suggest that neurotrophic factors have a protective role against amyloid beta toxicity.[84]

EpilepsyEdit

Epilepsy has also been linked with polymorphisms in BDNF. Given BDNF's vital role in the development of the landscape of the brain, there is quite a lot of room for influence on the development of neuropathologies from BDNF. Levels of both BDNF mRNA and BDNF protein are known to be up-regulated in epilepsy.[85] BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor-mediated post-synaptic currents.[86] This provides a potential mechanism for the observed up-regulation.

AgingEdit

BDNF levels appear to be highly regulated throughout the lifetime both in the early developmental stages and in the later stages of life. For example, BDNF appears to be critical for the morphological development such as dendrite orientation and number along with soma size.[87] This is important as neuron morphology is critical in behavioral processes like learning and motor skills development. Research has reported that the interaction between BDNF and TrkB (the receptor to BDNF) is highly important in inducing dendritic growth; some have noted that the phosphorylation of TrkB by another molecule, cdk5 is necessary for this interaction to occur.[88] Thus, high BDNF and active TrkB interaction appears to be necessary during a critical developmental period as it is regulatory in neuron morphology.

Although BDNF is needed in the developmental stages, BDNF levels have been shown to decrease in tissues with aging.[89] Studies using human subjects have found that hippocampal volume decreases with decreasing plasma levels of BDNF.[90] Although this does not mean BDNF necessarily impacts hippocampal volume, it does suggest there is a relationship that might explain some of the cognitive decline that occurs during aging.

MiscellaneousEdit

Variants close to the BDNF gene were found to be associated with obesity in two very large genome-wide association studies of body mass index (BMI).[91][92]

High levels of BDNF and Substance P have been associated with increased itching in eczema.[93]

BDNF is a regulator of drug addiction and psychological dependence. Animals chronically exposed to drugs of abuse show increased levels of BDNF in the ventral tegmental area (VTA) of the brain, and when BDNF is injected directly into the VTA of rats, the animals act as if they are addicted to and psychologically dependent upon opiates.[73]

BDNF is a short-term promoter,[94] but a long-term inhibitor of pain sensitivity, as a result of its effect as inducer of neuronal differentiation.[95] The polymorphism Thr2Ile may be linked to congenital central hypoventilation syndrome.[96][97] BDNF and IL-6 might be involved in the pathogenesis of post-chemotherapy cognitive impairment (PCCI, also known as chemo brain) and fatigue.[98]

ReferencesEdit

  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:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Binder DK, Scharfman HE (September 2004). "Brain-derived neurotrophic factor". Growth Factors. 22 (3): 123–31. PMC 2504526 . PMID 15518235. doi:10.1080/08977190410001723308. 
  6. ^ 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): 8060–4. Bibcode:1990PNAS...87.8060J. PMC 54892 . PMID 2236018. doi:10.1073/pnas.87.20.8060. 
  7. ^ a b Maisonpierre PC, Le Beau MM, Espinosa R, Ip NY, Belluscio L, de la Monte SM, Squinto S, Furth ME, Yancopoulos GD (July 1991). "Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations". Genomics. 10 (3): 558–68. PMID 1889806. doi:10.1016/0888-7543(91)90436-I. 
  8. ^ Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM (March 1995). "A BDNF autocrine loop in adult sensory neurons prevents cell death". Nature. 374 (6521): 450–3. Bibcode:1995Natur.374..450A. PMID 7700353. doi:10.1038/374450a0. 
  9. ^ Huang EJ, Reichardt LF (2001). "Neurotrophins: roles in neuronal development and function". Annual Review of Neuroscience. 24: 677–736. PMC 2758233 . PMID 11520916. doi:10.1146/annurev.neuro.24.1.677. 
  10. ^ Yamada K, Nabeshima T (April 2003). "Brain-derived neurotrophic factor/TrkB signaling in memory processes". Journal of Pharmacological Sciences. 91 (4): 267–70. PMID 12719654. doi:10.1254/jphs.91.267. 
  11. ^ 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. PMC 2716651 . PMID 19467646. doi:10.1016/j.archoralbio.2009.04.005. 
  12. ^ a b Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (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): 2711–6. Bibcode:2008PNAS..105.2711B. PMC 2268201 . PMID 18263738. doi:10.1073/pnas.0711863105. 
  13. ^ a b 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. PMID 9675054. doi:10.1006/mcne.1998.0684. 
  14. ^ a b 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. PMID 11517261. 
  15. ^ 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. PMID 11517260. 
  16. ^ 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. 
  17. ^ MGI database: phenotypes for BDNF homozygous null mice. http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537&int:_Set_key=847156
  18. ^ 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. PMC 4314337 . PMID 25455510. doi:10.1016/j.jpsychires.2014.10.003. 
  19. ^ Denham J, Marques FZ, O'Brien BJ, Charchar FJ (February 2014). "Exercise: putting action into our epigenome". Sports Medicine. 44 (2): 189–209. PMID 24163284. doi:10.1007/s40279-013-0114-1. 
  20. ^ 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. PMC 4064707 . PMID 24999318. doi:10.3389/fncel.2014.00170. 
  21. ^ 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. PMID 25362636. doi:10.1152/physiol.00067.2013. 
  22. ^ 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. PMC 4192966 . PMID 25317166. doi:10.4103/1673-5374.139475. 
  23. ^ Patapoutian A, Reichardt LF (June 2001). "Trk receptors: mediators of neurotrophin action". Current Opinion in Neurobiology. 11 (3): 272–80. PMID 11399424. doi:10.1016/S0959-4388(00)00208-7. 
  24. ^ 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): 5611–8. PMID 18495895. doi:10.1523/JNEUROSCI.5378-07.2008. 
  25. ^ Fatemi, S. Hossein (2008). Reelin Glycoprotein: Structure, Biology and Roles in Health and Disease. Berlin: Springer. pp. 444 pages. ISBN 978-0-387-76760-4. ; see the chapter "A Tale of Two Genes: Reelin and BDNF"; pp. 237–245
  26. ^ Ringstedt T, Linnarsson S, Wagner J, Lendahl U, Kokaia Z, Arenas E, Ernfors P, Ibáñez CF (August 1998). "BDNF regulates reelin expression and Cajal-Retzius cell development in the cerebral cortex". Neuron. 21 (2): 305–15. PMID 9728912. doi:10.1016/S0896-6273(00)80540-1. 
  27. ^ 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. PMID 18003743. doi:10.1242/dev.008227. 
  28. ^ Michaelsen K, Zagrebelsky M, Berndt-Huch J, Polack M, Buschler A, Sendtner M, Korte M (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. PMID 20955473. doi:10.1111/j.1460-9568.2010.07460.x. 
  29. ^ 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. PMC 2722960 . PMID 19418634. doi:10.1016/j.neuint.2009.01.006. 
  30. ^ Kuzumaki N, Ikegami D, Tamura R, Hareyama N, Imai S, Narita M, Torigoe K, Niikura K, Takeshima H, Ando T, Igarashi K, Kanno J, Ushijima T, Suzuki T, Narita M (February 2011). "Hippocampal epigenetic modification at the brain-derived neurotrophic factor gene induced by an enriched environment". Hippocampus. 21 (2): 127–32. PMID 20232397. doi:10.1002/hipo.20775. 
  31. ^ 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. PMID 9581763. doi:10.1016/s0896-6273(00)81010-7. 
  32. ^ 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. PMID 18234890. doi:10.1523/JNEUROSCI.2262-07.2008. 
  33. ^ 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. PMC 3802523 . PMID 22827965. doi:10.1017/S1461145712000685. 
  34. ^ Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (January 2003). "The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function". Cell. 112 (2): 257–69. PMID 12553913. doi:10.1016/S0092-8674(03)00035-7. 
  35. ^ 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. PMID 16869232. doi:10.3758/CABN.6.1.79. 
  36. ^ 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. PMC 3812868 . PMID 24198753. doi:10.3389/fnins.2013.00188. 
  37. ^ Cunha C, Brambilla R, Thomas KL (2010-01-01). "A simple role for BDNF in learning and memory?". Frontiers in Molecular Neuroscience. 3: 1. PMC 2821174 . PMID 20162032. doi:10.3389/neuro.02.001.2010. 
  38. ^ 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. PMC 5089164 . PMID 27699937. doi:10.1002/da.22497. 
  39. ^ 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. PMID 23674053. doi:10.1038/nrn3505. 
  40. ^ Terracciano A, Piras MG, Lobina M, Mulas A, Meirelles O, Sutin AR, Chan W, Sanna S, Uda M, Crisponi L, Schlessinger D (December 2013). "Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association study". The World Journal of Biological Psychiatry. 14 (8): 583–9. PMC 3288597 . PMID 22047184. doi:10.3109/15622975.2011.616533. 
  41. ^ 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. PMID 15379998. doi:10.1111/j.1460-9568.2004.03656.x. 
  42. ^ a b 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. PMID 19244205. doi:10.3181/0804-RM-128. 
  43. ^ Namekata K, Harada C, Taya C, Guo X, Kimura H, Parada LF, Harada T (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. PMC 2867726 . PMID 20368433. doi:10.1073/pnas.0914514107. 
  44. ^ 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. PMID 9648856. doi:10.1046/j.1471-4159.1998.71010106.x. 
  45. ^ Nakazawa T, Komai S, Tezuka T, Hisatsune C, Umemori H, Semba K, Mishina M, Manabe T, Yamamoto T (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): 693–9. PMID 11024032. doi:10.1074/jbc.M008085200. 
  46. ^ 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. PMC 196664 . PMID 12663749. doi:10.1101/lm.56003. 
  47. ^ 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. PMC 15154 . PMID 9892651. doi:10.1073/pnas.96.2.435. 
  48. ^ 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. PMID 14706865. doi:10.1016/j.brainres.2003.10.030. 
  49. ^ Caldeira MV, Melo CV, Pereira DB, Carvalho R, Correia SS, Backos DS, Carvalho AL, Esteban JA, Duarte CB (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. PMID 17337442. doi:10.1074/jbc.M700607200. 
  50. ^ a b Wu K, Len GW, McAuliffe G, Ma C, Tai JP, Xu F, Black IB (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. PMID 15519688. doi:10.1016/j.molbrainres.2004.07.019. 
  51. ^ 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. PMID 12163512. 
  52. ^ Chou WH, Wang D, McMahon T, Qi ZH, Song M, Zhang C, Shokat KM, Messing RO (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. PMC 2994917 . PMID 20962217. doi:10.1523/JNEUROSCI.0270-10.2010. 
  53. ^ 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. PMID 21435558. doi:10.1016/j.neuron.2011.02.034. 
  54. ^ a b Matsuoka Y, Li X, Bennett V (June 2000). "Adducin: structure, function and regulation". Cellular and Molecular Life Sciences. 57 (6): 884–95. PMID 10950304. doi:10.1007/pl00000731. 
  55. ^ a b c Stevens RJ, Littleton JT (May 2011). "Synaptic growth: dancing with adducin". Current Biology. 21 (10): R402–5. PMID 21601803. doi:10.1016/j.cub.2011.04.020. 
  56. ^ 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. PMID 17515902. doi:10.1038/nn1903. 
  57. ^ Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V, Mains RE, Eipper BA (January 2001). "The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis". Neuron. 29 (1): 229–42. PMID 11182094. doi:10.1016/s0896-6273(01)00193-3. 
  58. ^ 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. PMID 10400703. doi:10.1074/jbc.274.29.20693. 
  59. ^ a b Bath KG, Akins MR, Lee FS (September 2012). "BDNF control of adult SVZ neurogenesis". Developmental Psychobiology. 54 (6): 578–89. PMC 3139728 . PMID 21432850. doi:10.1002/dev.20546. 
  60. ^ Zhao CT, Li K, Li JT, Zheng W, Liang XJ, Geng AQ, Li N, Yuan XB (December 2009). "PKCdelta regulates cortical radial migration by stabilizing the Cdk5 activator p35". Proceedings of the National Academy of Sciences of the United States of America. 106 (50): 21353–8. Bibcode:2009PNAS..10621353Z. PMC 2781735 . PMID 19965374. doi:10.1073/pnas.0812872106. 
  61. ^ van Praag H, Kempermann G, Gage FH (December 2000). "Neural consequences of environmental enrichment". Nature Reviews. Neuroscience. 1 (3): 191–8. PMID 11257907. doi:10.1038/35044558. 
  62. ^ a b Zhong L, Yan CH, Lu CQ, Xu J, Huang H, Shen XM (September 2009). "Calmodulin activation is required for the enhancement of hippocampal neurogenesis following environmental enrichment". Neurological Research. 31 (7): 707–13. PMID 19055875. doi:10.1179/174313209X380856. 
  63. ^ Dwivedi Y (2009). "Brain-derived neurotrophic factor: role in depression and suicide". Neuropsychiatric Disease and Treatment. 5: 433–49. PMC 2732010 . PMID 19721723. doi:10.2147/ndt.s5700. 
  64. ^ Brunoni AR, Lopes M, Fregni F (December 2008). "A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression". The International Journal of Neuropsychopharmacology. 11 (8): 1169–80. PMID 18752720. doi:10.1017/S1461145708009309. 
  65. ^ Xiu MH, Hui L, Dang YF, Hou TD, Zhang CX, Zheng YL, Chen DC, Kosten TR, Zhang XY (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. PMID 19720106. doi:10.1016/j.pnpbp.2009.08.011. 
  66. ^ Maina G, Rosso G, Zanardini R, Bogetto F, Gennarelli M, Bocchio-Chiavetto L (April 2010). "Serum levels of brain-derived neurotrophic factor in drug-naïve obsessive-compulsive patients: a case-control study". Journal of Affective Disorders. 122 (1–2): 174–8. PMID 19664825. doi:10.1016/j.jad.2009.07.009. 
  67. ^ Zuccato C, Cattaneo E (June 2009). "Brain-derived neurotrophic factor in neurodegenerative diseases". Nature Reviews. Neurology. 5 (6): 311–22. PMID 19498435. doi:10.1038/nrneurol.2009.54. 
  68. ^ Zajac MS, Pang TY, Wong N, Weinrich B, Leang LS, Craig JM, Saffery R, Hannan AJ (May 2010). "Wheel running and environmental enrichment differentially modify exon-specific BDNF expression in the hippocampus of wild-type and pre-motor symptomatic male and female Huntington's disease mice". Hippocampus. 20 (5): 621–36. PMID 19499586. doi:10.1002/hipo.20658. 
  69. ^ Zeev BB, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E, Vecsler M, Vecksler M, Christodoulou J (April 2009). "The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome". Neurology. 72 (14): 1242–7. PMC 2677489 . PMID 19349604. doi:10.1212/01.wnl.0000345664.72220.6a. 
  70. ^ Arancio O, Chao MV (June 2007). "Neurotrophins, synaptic plasticity and dementia". Current Opinion in Neurobiology. 17 (3): 325–30. PMID 17419049. doi:10.1016/j.conb.2007.03.013. 
  71. ^ Mercader JM, Fernández-Aranda F, Gratacòs M, Ribasés M, Badía A, Villarejo C, Solano R, González JR, Vallejo J, Estivill X (2007). "Blood levels of brain-derived neurotrophic factor correlate with several psychopathological symptoms in anorexia nervosa patients". Neuropsychobiology. 56 (4): 185–90. PMID 18337636. doi:10.1159/000120623. 
  72. ^ Kaplan AS, Levitan RD, Yilmaz Z, Davis C, Tharmalingam S, Kennedy JL (January 2008). "A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa". The International Journal of Eating Disorders. 41 (1): 22–8. PMID 17922530. doi:10.1002/eat.20474. 
  73. ^ a b Vargas-Perez H, Ting-A Kee R, Walton CH, Hansen DM, Razavi R, Clarke L, Bufalino MR, Allison DW, Steffensen SC, van der Kooy D (June 2009). "Ventral tegmental area BDNF induces an opiate-dependent-like reward state in naive rats". Science. 324 (5935): 1732–4. Bibcode:2009Sci...324.1732V. PMC 2913611 . PMID 19478142. doi:10.1126/science.1168501. 
  74. ^ Thoenen H, Sendtner M (November 2002). "Neurotrophins: from enthusiastic expectations through sobering experiences to rational therapeutic approaches". Nature Neuroscience. 5 Suppl: 1046–50. PMID 12403983. doi:10.1038/nn938. 
  75. ^ Xiong P, Zeng Y, Wu Q, Han Huang DX, Zainal H, Xu X, Wan J, Xu F, Lu J (August 2014). "Combining serum protein concentrations to diagnose schizophrenia: a preliminary exploration". The Journal of Clinical Psychiatry. 75 (8): e794–801. PMID 25191916. doi:10.4088/JCP.13m08772. 
  76. ^ 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. PMC 4035720 . PMID 24802307. doi:10.1038/tp.2014.26. 
  77. ^ Warner-Schmidt JL, Duman RS (2006). "Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment". Hippocampus. 16 (3): 239–49. PMID 16425236. doi:10.1002/hipo.20156. 
  78. ^ Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW (2000). "Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus". Neuroscience. 101 (2): 305–12. PMID 11074154. doi:10.1016/S0306-4522(00)00349-3. 
  79. ^ Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X, Li X (November 2006). "Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB". Brain Research. 1122 (1): 56–64. PMID 17022948. doi:10.1016/j.brainres.2006.09.009. 
  80. ^ Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M (July 2003). "Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants". Biological Psychiatry. 54 (1): 70–5. PMID 12842310. doi:10.1016/S0006-3223(03)00181-1. 
  81. ^ Okamoto T, Yoshimura R, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, Inoue Y, Ueda N, Nakamura J (July 2008). "Efficacy of electroconvulsive therapy is associated with changing blood levels of homovanillic acid and brain-derived neurotrophic factor (BDNF) in refractory depressed patients: a pilot study". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 32 (5): 1185–90. PMID 18403081. doi:10.1016/j.pnpbp.2008.02.009. 
  82. ^ a b Drzyzga ŁR, Marcinowska A, Obuchowicz E (June 2009). "Antiapoptotic and neurotrophic effects of antidepressants: a review of clinical and experimental studies". Brain Research Bulletin. 79 (5): 248–57. PMID 19480984. doi:10.1016/j.brainresbull.2009.03.009. 
  83. ^ Taylor SM (June 2008). "Electroconvulsive therapy, brain-derived neurotrophic factor, and possible neurorestorative benefit of the clinical application of electroconvulsive therapy". The Journal of ECT. 24 (2): 160–5. PMID 18580563. doi:10.1097/YCT.0b013e3181571ad0. 
  84. ^ Mattson MP (November 2008). "Glutamate and neurotrophic factors in neuronal plasticity and disease". Annals of the New York Academy of Sciences. 1144: 97–112. Bibcode:2008NYASA1144...97M. PMC 2614307 . PMID 19076369. doi:10.1196/annals.1418.005. 
  85. ^ 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. 
  86. ^ Tanaka T, Saito H, Matsuki N (May 1997). "Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus". The Journal of Neuroscience. 17 (9): 2959–66. PMID 9096132. 
  87. ^ Gorski JA, Zeiler SR, Tamowski S, Jones KR (July 2003). "Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites". The Journal of Neuroscience. 23 (17): 6856–65. PMID 12890780. 
  88. ^ Cheung ZH, Chin WH, Chen Y, Ng YP, Ip NY (April 2007). "Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons". PLoS Biology. 5 (4): e63. PMC 1808488 . PMID 17341134. doi:10.1371/journal.pbio.0050063. 
  89. ^ Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S (November 2008). "New insights into brain BDNF function in normal aging and Alzheimer disease". Brain Research Reviews. 59 (1): 201–20. PMID 18708092. doi:10.1016/j.brainresrev.2008.07.007. 
  90. ^ Erickson KI, Prakash RS, Voss MW, Chaddock L, Heo S, McLaren M, Pence BD, Martin SA, Vieira VJ, Woods JA, McAuley E, Kramer AF (April 2010). "Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume". The Journal of Neuroscience. 30 (15): 5368–75. PMC 3069644 . PMID 20392958. doi:10.1523/jneurosci.6251-09.2010. 
  91. ^ Thorleifsson G, Walters GB, Gudbjartsson DF, Steinthorsdottir V, Sulem P, Helgadottir A, et al. (January 2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity". Nature Genetics. 41 (1): 18–24. PMID 19079260. doi:10.1038/ng.274. 
  92. ^ Willer CJ, Speliotes EK, Loos RJ, Li S, Lindgren CM, Heid IM, et al. (January 2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nature Genetics. 41 (1): 25–34. PMC 2695662 . PMID 19079261. doi:10.1038/ng.287. 
  93. ^ "'Blood chemicals link' to eczema". BBC News. 26 August 2007. 
  94. ^ Shu XQ, Mendell LM (July 1999). "Neurotrophins and hyperalgesia". Proceedings of the National Academy of Sciences of the United States of America. 96 (14): 7693–6. PMC 33603 . PMID 10393882. doi:10.1073/pnas.96.14.7693. 
  95. ^ Rusanescu G, Mao J (October 2015). "Immature spinal cord neurons are dynamic regulators of adult nociceptive sensitivity". Journal of Cellular and Molecular Medicine. 19 (10): 2352–64. PMC 4594677 . PMID 26223362. doi:10.1111/jcmm.12648. 
  96. ^ Online Mendelian Inheritance in Man (OMIM) Brain-Derived Neurotrophic Factor; Bdnf -113505
  97. ^ Weese-Mayer DE, Bolk S, Silvestri JM, Chakravarti A (February 2002). "Idiopathic congenital central hypoventilation syndrome: evaluation of brain-derived neurotrophic factor genomic DNA sequence variation". American Journal of Medical Genetics. 107 (4): 306–10. PMID 11840487. doi:10.1002/ajmg.10133. 
  98. ^ Zimmer P, Mierau A, Bloch W, Strüder HK, Hülsdünker T, Schenk A, Fiebig L, Baumann FT, Hahn M, Reinart N, Hallek M, Elter T (February 2015). "Post-chemotherapy cognitive impairment in patients with B-cell non-Hodgkin lymphoma: a first comprehensive approach to determine cognitive impairments after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or rituximab and bendamustine". Leukemia & Lymphoma. 56 (2): 347–52. PMID 24738942. doi:10.3109/10428194.2014.915546. 

External linksEdit