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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/07 19:45:23」(JST)
wiki ja
脳由来神経栄養因子（のうゆらいしんけいえいよういんし、BDNF; Brain-derived neurotrophic factorとも）は、標的細胞表面上にある特異的受容体TrkBに結合し、神経細胞の生存・成長・シナプスの機能亢進などの神経細胞の成長を調節する脳細胞の増加には不可欠な神経系の液性蛋白質である。
現在、BDNFに関しては自閉症や痛風との関係等、神経疾患治療に応用可能な蛋白質として着目されている。 また、広島大学の栗原英見教授らによってBDNFが歯の関連細胞や血管の増殖、分化を促進することが発見され、歯周再生への関与が見いだされた。 すでに動物実験において、BDNFの投与した歯周病モデル動物が健常動物と同様の歯周の状態に回復させることに成功している。 一般開業医で可能な簡単な手術により、歯周病でダメージを受けた歯周を再生できる治療を目指し開発が進行中であり、国際特許出願をしている。
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wiki en
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PDB rendering based on 1bnd.[1] |
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| Identifiers | |||||||||||||
| Symbols | BDNF ; ANON2; BULN2 | ||||||||||||
| External IDs | OMIM: 113505 MGI: 88145 HomoloGene: 7245 GeneCards: BDNF Gene | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Species | Human | Mouse | |||||||||||
| Entrez | 627 | 12064 | |||||||||||
| Ensembl | ENSG00000176697 | ENSMUSG00000048482 | |||||||||||
| UniProt | P23560 | P21237 | |||||||||||
| RefSeq (mRNA) | NM_001143805 | NM_001048139 | |||||||||||
| RefSeq (protein) | NP_001137277 | NP_001041604 | |||||||||||
| Location (UCSC) | Chr 11: 27.68 – 27.74 Mb |
Chr 2: 109.67 – 109.73 Mb |
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| PubMed search | [1] | [2] | |||||||||||
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Brain-derived neurotrophic factor, also known as BDNF, is a protein[2] that, in humans, is encoded by the BDNF gene.[3][4] 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.
Contents
- 1 Function
- 2 Mechanism of action
- 2.1 TrkB
- 2.2 LNGFR
- 3 Expression
- 4 Role in synaptic transmission
- 4.1 Glutamatergic signaling
- 4.1.1 NMDA receptor activity
- 4.1.2 Synapse stability
- 4.2 GABAergic signaling
- 4.3 Synaptogenesis
- 4.4 Dendridogenesis
- 4.1 Glutamatergic signaling
- 5 Neurogenesis
- 6 Cognitive function
- 7 Disease linkage
- 7.1 Schizophrenia
- 7.2 Depression
- 7.3 Eczema
- 7.4 Epilepsy
- 7.5 Alzheimer's disease
- 7.6 Drug addiction and dependence
- 7.7 Obesity
- 7.8 Aging
- 7.9 Congenital central hypoventilation syndrome
- 7.10 Post-chemotherapy cognitive impairment
- 8 References
- 9 External links
Function
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.[5][6] In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking.[7] It is also expressed in the retina, motor neurons, the kidneys, saliva, and the prostate.[8]
BDNF itself is important for long-term memory.[9] 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 chemicals that help to stimulate and control neurogenesis, BDNF being one of the most active.[10][11][12] 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.[13] 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.[14]
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.[15][16][17][18] Niacin appears to upregulate BDNF and tropomyosin receptor kinase B (TrkB) expression as well.[19]
Mechanism of action
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).[20] It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor.[21] BDNF has also been shown to interact with the reelin signaling chain.[22] The expression of reelin by Cajal-Retzius cells goes down during development under the influence of BDNF.[23] The latter also decreases reelin expression in neuronal culture.
TrkB
The TrkB receptor is encoded by the NTRK2 gene and is member of a receptor family of tyrosine kinases that includes TrkA and TrkC. These receptors all interact with neurotrophins in a ligand-specific manner. TrkB autophosphorylation is dependent upon its ligand-specific association with BDNF, a widely expressed activity-dependent neurotrophic factor that regulates neuroplasticity and is upregulated following hypoxic injury.
LNGFR
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.[24] When the p75 receptor is activated, it leads to activation of NFkB receptor.[24] 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.[25]
Expression
The BDNF protein is encoded by a gene that is also called BDNF, found in humans on chromosome 11.[3][4] Structurally, BDNF transcription is controlled by 8 different promoters, each leading to different transcripts containing one of the 8 untranslated 5’ promoter exons spliced to the 3’ encoding exon. Promoter IV activity 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 .[26] There are multiple mechanisms through neuronal activity can increase BDNF exon IV specific expression.[26] 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.[26][27] 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.[28] 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).[29] 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.[29] Activation of Dopamine receptor D5 also promotes expression of BDNF in prefrontal cortex neurons.[30]
Val66Met (rs6265) is a single nucleotide polymorphism in the gene where adenine and guanine alleles vary, resulting in a variation between valine and methionine at codon 66.[31][32] As of 2008, Val66Met is probably the most investigated SNP of the BDNF gene, but, besides this variant, other SNPs in the gene are C270T, rs7103411, rs2030324, rs2203877, rs2049045 and rs7124442.
Role in synaptic transmission
Glutamatergic signaling
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 activity
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.[33][34] 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.[33] 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.[33] PI3 kinase and Akt are also essential in BDNF-induced potentiation of NMDA receptor function and inhibition of either molecule completely eliminated receptor activity.[34] 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.[35][36] Once activated, Fyn can bind to NR2B through its SH2 domain and mediate phosphorylation of its Tyr-1472 site.[37] Similar studies have suggested Fyn is also capable of activating NR2A although this was not found in the hippocampus.[38][39] 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.[38]
Synapse stability
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.[40] 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.[41] It also appears that BDNF is able to influence Gl1 activity through its effects on NMDA receptor activity.[42] 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.[42] 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
One mechanism through which BDNF appears to maintain elevated levels of neuronal excitation is through preventing GABAergic signaling activities.[43] While glutamate is the brain’s major excitatory neurotransmitter and phosphorylation normally activates receptors, GABA is the brain’s primary inhibitory neurotransmitter and phoshorylation 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).[43] Similar effects could be obtained in BDNF knockout mice, but these effects were reversed by local application of BDNF.[43] 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.[43] Once activated, PKC can reduce the amplitude of IPSCs through to GABAA receptor phosphorylation and inhibition.[43] 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.[44]
Synaptogenesis
BDNF is also enhances synaptogenesis. Synaptogenesis is dependent upon the assembly of new synapses and the disassembly of old synapses by β-adducin.[45] 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.[46] 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.[47] In post-synaptic neurons they can influence dendritic spine formation and retraction as well as AMPA receptor insertion and removal.[47] At their C-terminus, adducins possess a myristoylated alanine-rich C kinase substrate (MARCKS) domain which regulates their capping activity.[46] 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.[45][47]
Dendridogenesis
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.[48] 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.[49] Thus, BDNF-induced trafficking of PSD-95 to dendrites stimulates actin remodeling and causes dendritic growth in response to BDNF.
Neurogenesis
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.[24] 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.[24] BDNF can also promote NSC and NPC proliferation through Akt activation and PTEN inactivation.[50] There have been many in vivo studies demonstrating BDNF is a strong promoter of neuronal differentiation.[24][51] 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.[10][11][51] 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.[52]
Cognitive function
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.[53][54] 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.[54] 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 linkage
See also: Neuroplasticity and Neurobiological effects of physical exercise § BDNF signaling
Various studies have shown possible links between BDNF and conditions, such as depression,[55][56] schizophrenia,[57] obsessive-compulsive disorder,[58] Alzheimer's disease,[59] Huntington's disease,[60] Rett syndrome,[61] and dementia,[62] as well as anorexia nervosa[63] and bulimia nervosa.[64] Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when expressed in the ventral tegmental area in rats.[65]
Schizophrenia
A plethora of recent evidence suggests the linkage between schizophrenia and BDNF.[66] 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.[67] 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.[68] 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.
Depression
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.[69] 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,[70] caloric restriction, intellectual stimulation, curcumin[71] and various treatments for depression (such as antidepressants[72] and electroconvulsive therapy[73]) increase expression of BDNF in the brain. In the case of some treatments such as drugs[74] and electroconvulsive therapy[75] this has been shown to protect or reverse this atrophy.[74]
Eczema
High levels of BDNF and Substance P have been associated with increased itching in eczema.[76]
Epilepsy
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.[77] BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor-mediated post-synaptic currents.[78] This provides a potential mechanism for the observed up-regulation.
Alzheimer's disease
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.[79]
Drug addiction and dependence
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.[80]
Obesity
In 2009, 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).[81][82]
Aging
BDNF levels decrease during aging.[83]
Congenital central hypoventilation syndrome
The polymorphism Thr2Ile may be linked to congenital central hypoventilation syndrome.[84][85]
Post-chemotherapy cognitive impairment
BDNF and IL-6 might be involved in the pathogenesis of post-chemotherapy cognitive impairment (PCCI, also known as chemo brain) and fatigue.[86]
References
- ^ Robinson RC, Radziejewski C, Stuart DI, Jones EY (April 1995). "Structure of the brain-derived neurotrophic factor/neurotrophin 3 heterodimer". Biochemistry 34 (13): 4139–46. doi:10.1021/bi00013a001. PMID 7703225.
- ^ Binder DK, Scharfman HE (September 2004). "Brain-derived Neurotrophic Factor". Growth Factors 22 (3): 123–31. doi:10.1080/08977190410001723308. PMC 2504526. PMID 15518235.
- ^ a b Jones KR, Reichardt LF (October 1990). "Molecular cloning of a human gene that is a member of the nerve growth factor family". Proc. Natl. Acad. Sci. U.S.A. 87 (20): 8060–4. doi:10.1073/pnas.87.20.8060. PMC 54892. PMID 2236018.
- ^ 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.
- ^ 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): 450–3. doi:10.1038/374450a0. PMID 7700353.
- ^ Huang EJ, Reichardt LF (2001). "Neurotrophins: Roles in Neuronal Development and Function". Annu. Rev. Neurosci. 24: 677–736. doi:10.1146/annurev.neuro.24.1.677. PMC 2758233. PMID 11520916.
- ^ Yamada K, Nabeshima T (April 2003). "Brain-derived neurotrophic factor/TrkB signaling in memory processes". J. Pharmacol. Sci. 91 (4): 267–70. doi:10.1254/jphs.91.267. PMID 12719654.
- ^ Mandel AL, Ozdener H, Utermohlen V (July 2009). "Identification of Pro- and Mature Brain-derived Neurotrophic Factor in Human Saliva". Arch. Oral Biol. 54 (7): 689–95. doi:10.1016/j.archoralbio.2009.04.005. PMC 2716651. PMID 19467646.
- ^ 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". Proc. Natl. Acad. Sci. U.S.A. 105 (7): 2711–6. doi:10.1073/pnas.0711863105. PMC 2268201. PMID 18263738.
- ^ 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". Mol. Cell. Neurosci. 11 (4): 234–45. doi:10.1006/mcne.1998.0684. PMID 9675054.
- ^ a b Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA (1 September 2001). "Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain". J. Neurosci. 21 (17): 6718–31. PMID 11517261.
- ^ Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (1 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". J. Neurosci. 21 (17): 6706–17. PMID 11517260.
- ^ 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". Int. J. Dev. Biol. 39 (5): 799–807. PMID 8645564.
- ^ MGI database: phenotypes for BDNF homozygous null mice. http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537&int:_Set_key=847156
- ^ Szuhany KL, Bugatti M, Otto MW (October 2014). "A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor". J Psychiatr Res 60C: 56–64. doi:10.1016/j.jpsychires.2014.10.003. PMID 25455510.
Consistent evidence indicates that exercise improves cognition and mood, with preliminary evidence suggesting that brain-derived neurotrophic factor (BDNF) may mediate these effects. The aim of the current meta-analysis was to provide an estimate of the strength of the association between exercise and increased BDNF levels in humans across multiple exercise paradigms. We conducted a meta-analysis of 29 studies (N = 1111 participants) examining the effect of exercise on BDNF levels in three exercise paradigms: (1) a single session of exercise, (2) a session of exercise following a program of regular exercise, and (3) resting BDNF levels following a program of regular exercise. Moderators of this effect were also examined. Results demonstrated a moderate effect size for increases in BDNF following a single session of exercise (Hedges' g = 0.46, p < 0.001). Further, regular exercise intensified the effect of a session of exercise on BDNF levels (Hedges' g = 0.59, p = 0.02). Finally, results indicated a small effect of regular exercise on resting BDNF levels (Hedges' g = 0.27, p = 0.005). ... Effect size analysis supports the role of exercise as a strategy for enhancing BDNF activity in humans
- ^ Denham J, Marques FZ, O'Brien BJ, Charchar FJ (February 2014). "Exercise: putting action into our epigenome". Sports Med 44 (2): 189–209. doi:10.1007/s40279-013-0114-1. PMID 24163284.
Aerobic physical exercise produces numerous health benefits in the brain. Regular engagement in physical exercise enhances cognitive functioning, increases brain neurotrophic proteins, such as brain-derived neurotrophic factor (BDNF), and prevents cognitive diseases [76–78]. Recent findings highlight a role for aerobic exercise in modulating chromatin remodelers [21, 79–82]. ... These results were the first to demonstrate that acute and relatively short aerobic exercise modulates epigenetic modifications. The transient epigenetic modifications observed due to chronic running training have also been associated with improved learning and stress-coping strategies, epigenetic changes and increased c-Fos-positive neurons ... Nonetheless, these studies demonstrate the existence of epigenetic changes after acute and chronic exercise and show they are associated with improved cognitive function and elevated markers of neurotrophic factors and neuronal activity (BDNF and c-Fos). ... The aerobic exercise training-induced changes to miRNA profile in the brain seem to be intensity-dependent [164]. These few studies provide a basis for further exploration into potential miRNAs involved in brain and neuronal development and recovery via aerobic exercise.
- ^ Phillips C, Baktir MA, Srivatsan M, Salehi A (2014). "Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling". Front Cell Neurosci 8: 170. doi:10.3389/fncel.2014.00170. PMC 4064707. PMID 24999318.
Moreover, recent evidence suggests that myokines released by exercising muscles affect the expression of brain-derived neurotrophic factor synthesis in the dentate gyrus of the hippocampus, a finding that could lead to the identification of new and therapeutically important mediating factors. ... Studies have demonstrated the intensity of exercise training is positively correlated with BDNF plasma levels in young, healthy individuals (Ferris et al., 2007). Resistance exercise has also been shown to elevate serum BDNF levels in young individuals (Yarrow et al., 2010). Moreover, it has been shown that moderate levels of physical activity in people with AD significantly increased plasma levels of BDNF (Coelho et al., 2014). ... In humans, it has been shown that 4 h of rowing activity leads to increased levels of plasma BDNF from the internal jugular (an indicator of central release from the brain) and radial artery (an indicator of peripheral release; Rasmussen et al., 2009). Seifert et al. (2010) reported that basal release of BDNF increases following 3 months endurance training in young and healthy individuals, as measured from the jugular vein. These trends are augmented by rodent studies showing that endurance training leads to increased synthesis of BDNF in the hippocampal formation (Neeper et al., 1995, 1996). ... Both BDNF and IGF-1 play a significant role in cognition and motor function in humans. ... Multiple large-scale studies in humans have shown that serum levels of IGF-1 are correlated with fitness and as well as body mass indices (Poehlman and Copeland, 1990). Furthermore, animal studies have shown that exercise in rats is associated with increased amounts of IGF-1 in the CSF.
- ^ 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 (Bethesda) 29 (6): 421–436. doi:10.1152/physiol.00067.2013. PMID 25362636.
The Effects of Acute Exercise
Studies in humans and animals have shown that brain blood flow remains largely unchanged in response to acute exercise[,] ... does not increase with increasing exercise intensity[, and] ... increased metabolic demands of active brain parts are mostly met by redistributing oxygen supply, although changes in oxygen extraction may also contribute. During exercise, blood flow is directed to the areas controlling locomotor, vestibular, cardiorespiratory, and visual functions (8, 91), facilitated by direct communication of neurons and vascular cells (94, 134). ... with increasing exercise intensity, brain glucose uptake decreases (75) as the uptake and utilization of lactate is enhanced (65, 139, 182). Regional differences in brain glucose uptake are also evident, which is furthermore influenced by the level of physical fitness. Thus the decrease in glucose uptake in the dorsal part of the anterior cingulate cortex during exercise is significantly more pronounced in subjects with higher exercise capacity (75) ...
The Effects of Long-Term Exercise Training
[A] physically active lifestyle has been shown to lead to higher cognitive performance and delayed or prevented neurological conditions in humans (71, 101, 143, 191). ... The production of brain-derived neurotrophic factor (BDNF), a key protein regulating maintenance and growth of neurons, is known to be stimulated by acute exercise (145), which may contribute to learning and memory. BDNF is released from brain already at rest but increases two- to threefold during exercise, which contributes 70–80% of circulating BDNF (145). - ^ Fu L, Doreswamy V, Prakash R (2014). "The biochemical pathways of central nervous system neural degeneration in niacin deficiency". Neural Regen Res 9 (16): 1509–1513. doi:10.4103/1673-5374.139475. PMC 4192966. PMID 25317166.
Recent evidences suggest that niacin administration may up-regulate the expression of BDNF-TrkB. ... At present, we can safely raise the possibility that niacin-mediated neural growth by the BDNF-TrkB pathway could be at least partially mediated by enhanced HDL-C levels.
- ^ Patapoutian A, Reichardt LF (June 2001). "Trk receptors: mediators of neurotrophin action". Curr. Opin. Neurobiol. 11 (3): 272–80. doi:10.1016/S0959-4388(00)00208-7. PMID 11399424.
- ^ 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". J. Neurosci. 28 (21): 5611–8. doi:10.1523/JNEUROSCI.5378-07.2008. PMID 18495895.
- ^ 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
- ^ 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.
- ^ a b c d e Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, Miller FD (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.
- ^ Michaelsen K, Zagrebelsky M, Berndt-Huch J, Polack M, Buschler A, Sendtner M et al. (2010). "Neurotrophin receptors TrkB.T1 and p75NTR cooperate in modulating both functional and structural plasticity in mature hippocampal neurons". Eur. J. Neurosci. 32 (11): 1854–65. doi:10.1111/j.1460-9568.2010.07460.x. PMID 20955473.
- ^ a b c Zheng F, Wang H (2009). "NMDA-mediated and self-induced bdnf exon IV transcriptions are differentially regulated in cultured cortical neurons". Neurochem. Int. 54 (5–6): 385–92. doi:10.1016/j.neuint.2009.01.006. PMC 2722960. PMID 19418634.
- ^ Kuzumaki N, Ikegami D, Tamura R, Hareyama N, Imai S, Narita M et al. (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.
- ^ Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME (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.
- ^ 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". J. Neurosci. 28 (5): 1118–30. doi:10.1523/JNEUROSCI.2262-07.2008. PMID 18234890.
- ^ Perreault ML, Jones-Tabah J, O'Dowd BF, George SR (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.
- ^ 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.
- ^ Bath KG, Lee FS (March 2006). "Variant BDNF (Val66Met) impact on brain structure and function". Cogn Affect Behav Neurosci 6 (1): 79–85. doi:10.3758/CABN.6.1.79. PMID 16869232.
- ^ 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". Eur. J. Neurosci. 20 (7): 1769–78. doi:10.1111/j.1460-9568.2004.03656.x. PMID 15379998.
- ^ a b Xu X, Ye L, Ruan Q (March 2009). "Environmental enrichment induces synaptic structural modification after transient focal cerebral ischemia in rats". Exp. Biol. Med. (Maywood) 234 (3): 296–305. doi:10.3181/0804-RM-128. PMID 19244205.
- ^ Namekata K, Harada C, Taya C, Guo X, Kimura H, Parada LF et al. (2010). "Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex". Proc. Natl. Acad. Sci. U.S.A. 107 (16): 7586–91. doi:10.1073/pnas.0914514107. PMC 2867726. PMID 20368433.
- ^ Iwasaki Y, Gay B, Wada K, Koizumi S (1998). "Association of the Src family tyrosine kinase Fyn with TrkB". J. Neurochem. 71 (1): 106–11. doi:10.1046/j.1471-4159.1998.71010106.x. PMID 9648856.
- ^ Nakazawa T, Komai S, Tezuka T, Hisatsune C, Umemori H, Semba K et al. (2001). "Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor". J. Biol. Chem. 276 (1): 693–9. doi:10.1074/jbc.M008085200. PMID 11024032.
- ^ a b Mizuno M, Yamada K, He J, Nakajima A, Nabeshima T (2003). "Involvement of BDNF receptor TrkB in spatial memory formation". Learn. Mem. 10 (2): 108–15. doi:10.1101/lm.56003. PMC 196664. PMID 12663749.
- ^ Tezuka T, Umemori H, Akiyama T, Nakanishi S, Yamamoto T (1999). "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A". Proc. Natl. Acad. Sci. U.S.A. 96 (2): 435–40. doi:10.1073/pnas.96.2.435. PMC 15154. PMID 9892651.
- ^ Briones TL, Suh E, Jozsa L, Hattar H, Chai J, Wadowska M (2004). "Behaviorally-induced ultrastructural plasticity in the hippocampal region after cerebral ischemia". Brain Res. 997 (2): 137–46. doi:10.1016/j.brainres.2003.10.030. PMID 14706865.
- ^ Caldeira MV, Melo CV, Pereira DB, Carvalho R, Correia SS, Backos DS et al. (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". J. Biol. Chem. 282 (17): 12619–28. doi:10.1074/jbc.M700607200. PMID 17337442.
- ^ a b Wu K, Len GW, McAuliffe G, Ma C, Tai JP, Xu F et al. (2004). "Brain-derived neurotrophic factor acutely enhances tyrosine phosphorylation of the AMPA receptor subunit GluR1 via NMDA receptor-dependent mechanisms". Brain Res. Mol. Brain Res. 130 (1–2): 178–86. doi:10.1016/j.molbrainres.2004.07.019. PMID 15519688.
- ^ a b c d e Henneberger C, Jüttner R, Rothe T, Grantyn R (2002). "Postsynaptic action of BDNF on GABAergic synaptic transmission in the superficial layers of the mouse superior colliculus". J. Neurophysiol. 88 (2): 595–603. PMID 12163512.
- ^ Chou WH, Wang D, McMahon T, Qi ZH, Song M, Zhang C et al. (2010). "GABAA receptor trafficking is regulated by protein kinase C(epsilon) and the N-ethylmaleimide-sensitive factor". J. Neurosci. 30 (42): 13955–65. doi:10.1523/JNEUROSCI.0270-10.2010. PMC 2994917. PMID 20962217.
- ^ a b Bednarek E, Caroni P (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.
- ^ a b Matsuoka Y, Li X, Bennett V (June 2000). "Adducin: structure, function and regulation". Cell. Mol. Life Sci. 57 (6): 884–95. doi:10.1007/pl00000731. PMID 10950304.
- ^ a b c Stevens RJ, Littleton JT (2011). "Synaptic growth: dancing with adducin". Curr. Biol. 21 (10): R402–5. doi:10.1016/j.cub.2011.04.020. PMID 21601803.
- ^ Yoshii A, Constantine-Paton M (2007). "BDNF induces transport of PSD-95 to dendrites through PI3K-AKT signaling after NMDA receptor activation". Nat. Neurosci. 10 (6): 702–11. doi:10.1038/nn1903. PMID 17515902.
- ^ Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V et al. (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.
- ^ Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM (1999). "PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/Akt cell survival pathway". J. Biol. Chem. 274 (29): 20693–703. doi:10.1074/jbc.274.29.20693. PMID 10400703.
- ^ a b Bath KG, Akins MR, Lee FS (2012). "BDNF control of adult SVZ neurogenesis". Dev Psychobiol 54 (6): 578–89. doi:10.1002/dev.20546. PMC 3139728. PMID 21432850.
- ^ Zhao CT, Li K, Li JT, Zheng W, Liang XJ, Geng AQ et al. (2009). "PKCdelta regulates cortical radial migration by stabilizing the Cdk5 activator p35". Proc. Natl. Acad. Sci. U.S.A. 106 (50): 21353–8. doi:10.1073/pnas.0812872106. PMC 2781735. PMID 19965374.
- ^ van Praag H, Kempermann G, Gage FH (2000). "Neural consequences of environmental enrichment". Nat. Rev. Neurosci. 1 (3): 191–8. doi:10.1038/35044558. PMID 11257907.
- ^ a b Zhong L, Yan CH, Lu CQ, Xu J, Huang H, Shen XM (2009). "Calmodulin activation is required for the enhancement of hippocampal neurogenesis following environmental enrichment". Neurol. Res. 31 (7): 707–13. doi:10.1179/174313209X380856. PMID 19055875.
- ^ Dwivedi Y (2009). "Brain-derived neurotrophic factor: role in depression and suicide". Neuropsychiatr Dis Treat 5: 433–49. doi:10.2147/ndt.s5700. PMC 2732010. PMID 19721723.
- ^ 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): 1169–1180. doi:10.1017/S1461145708009309. ISSN 1461-1457. PMID 18752720.
- ^ Xiu MH, Hui L, Dang YF, Hou TD, Zhang CX, Zheng YL et al. (August 2009). "Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics". Prog. Neuropsychopharmacol. Biol. Psychiatry 33 (8): 1508–12. doi:10.1016/j.pnpbp.2009.08.011. PMID 19720106.
- ^ Maina G, Rosso G, Zanardini R, Bogetto F, Gennarelli M, Bocchio-Chiavetto L (August 2009). "Serum levels of brain-derived neurotrophic factor in drug-na?ve obsessive-compulsive patients: A case-control study". J Affect Disord 122 (1–2): 174–8. doi:10.1016/j.jad.2009.07.009. PMID 19664825.
- ^ Zuccato C, Cattaneo E (June 2009). "Brain-derived neurotrophic factor in neurodegenerative diseases". Nat Rev Neurol 5 (6): 311–22. doi:10.1038/nrneurol.2009.54. PMID 19498435.
- ^ Zajac MS, Pang TY, Wong N, Weinrich B, Leang LS, Craig JM et al. (June 2009). "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. doi:10.1002/hipo.20658. PMID 19499586.
- ^ Zeev BB, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E et al. (April 2009). "The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome". Neurology 72 (14): 1242–7. doi:10.1212/01.wnl.0000345664.72220.6a. PMC 2677489. PMID 19349604.
- ^ Arancio O, Chao MV (June 2007). "Neurotrophins, synaptic plasticity and dementia". Curr. Opin. Neurobiol. 17 (3): 325–30. doi:10.1016/j.conb.2007.03.013. PMID 17419049.
- ^ Mercader JM, Fernández-Aranda F, Gratacòs M, Ribasés M, Badía A, Villarejo C et al. (2007). "Blood levels of brain-derived neurotrophic factor correlate with several psychopathological symptoms in anorexia nervosa patients". Neuropsychobiology 56 (4): 185–90. doi:10.1159/000120623. PMID 18337636.
- ^ 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". Int J Eat Disord 41 (1): 22–8. doi:10.1002/eat.20474. PMID 17922530.
- ^ Vargas-Perez H, Ting-A Kee R, Walton CH, Hansen DM, Razavi R, Clarke L et al. (June 2009). "Ventral Tegmental Area BDNF Induces an Opiate-Dependent–Like Reward State in Naïve Rats". Science 324 (5935): 1732–34. doi:10.1126/science.1168501. PMC 2913611. PMID 19478142.
- ^ Xiong P, Zeng Y, Wu Q, Han Huang DX, Zainal H, Xu X et al. (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.
- ^ Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A et al. (2008). "BDNF is essential to promote persistence of long-term memory storage". Proceedings of the National Academy of Sciences 105 (7): 2711–6. doi:10.1073/pnas.0711863105. PMC 2268201. PMID 18263738.
- ^ Ray MT, Shannon Weickert C, Webster MJ (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.
- ^ Warner-Schmidt JL, Duman RS (2006). "Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment". Hippocampus 16 (3): 239–49. doi:10.1002/hipo.20156. PMID 16425236.
- ^ 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. doi:10.1016/S0306-4522(00)00349-3. PMID 11074154.
- ^ Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X et al. (2006). "Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB". Brain Research 1122 (1): 56–56. doi:10.1016/j.brainres.2006.09.009. PMID 17022948.
- ^ Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C et al. (2003). "Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants". Biol Psychiatry 54 (1): 70–5. doi:10.1016/S0006-3223(03)00181-1. PMID 12842310.
- ^ Okamoto T, Yoshimura R, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, Inoue Y et al. (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". Prog Neuropsychopharmacol Biol Psychiatry 32 (5): 1185–90. doi:10.1016/j.pnpbp.2008.02.009. PMID 18403081. Cite uses deprecated parameter
|author-separator=(help) - ^ 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. doi:10.1016/j.brainresbull.2009.03.009. PMID 19480984. Cite uses deprecated parameter
|author-separator=(help) - ^ 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. doi:10.1097/YCT.0b013e3181571ad0. PMID 18580563. Cite uses deprecated parameter
|author-separator=(help) - ^ "'Blood chemicals link' to eczema". BBC News. 26 August 2007.
- ^ 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 Res Suppl 4: 225–45. PMID 1815605.
- ^ Tanaka T, Saito H, Matsuki N (1 May 1997). "Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus". J Neurosci 17 (9): 2959–66. PMID 9096132.
- ^ Mattson MP (November 2008). "Glutamate and Neurotrophic Factors in Neuronal Plasticity and Disease". Annals of the New York Academy of Sciences 1144: 97–90. Bibcode:2008NYASA1144...97M. doi:10.1196/annals.1418.005. ISSN 0077-8923. PMC 2614307. PMID 19076369.
- ^ Stram DO, Mizuno S (2009). "Ventral Tegmental Area BDNF Induces an Opiate-Dependent–Like Reward State in Naïve Rats.". Science. doi:10.1126/science.1168501. PMC 2913611. PMID 2913611.
- ^ 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". Nat. Genet. 41 (1): 18–24. doi:10.1038/ng.274. PMID 19079260.
- ^ 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". Nat. Genet. 41 (1): 24–34. doi:10.1038/ng.287. PMC 2695662. PMID 19079261.
- ^ Tapia-Arancibia L, Aliaga E, Silhol M, Arancibia S (2008). "New insights into brain BDNF function in normal aging and Alzheimer disease". Brain Res Rev 59 (1): 201–20. doi:10.1016/j.brainresrev.2008.07.007. PMID 18708092.
- ^ Online 'Mendelian Inheritance in Man' (OMIM) Brain-Derived Neurotrophic Factor; Bdnf -113505
- ^ Weese-Mayer DE, Bolk S, Silvestri JM, Chakravarti A (2002). "Idiopathic congenital central hypoventilation syndrome: evaluation of brain-derived neurotrophic factor genomic DNA sequence variation". Am. J. Med. Genet. 107 (4): 306–310. doi:10.1002/ajmg.10133. PMID 11840487.
- ^ Zimmer P, Mierau A, Bloch W, Strüder HK, Hülsdünker T, Schenk A et al. (2014). "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". Leuk. Lymphoma: 1–6. doi:10.3109/10428194.2014.915546. PMID 24738942.
External links
- Cotman CW, Berchtold NC (28 January 2004). "BDNF and Alzheimer's Disease—What's the Connection?". Alzforum: Live Discussions. Alzheimer Research Forum. Retrieved 21 August 2008.
- Patten-Hitt E (14 June 2001). "Brain-Derived Neurotrophic Factor (BDNF)". Sciencexpress. The HDLighthouse, Huntingtons Disease: Information and Community. Retrieved 21 August 2008.
- Highfield R (18 October 2007). "Brain scans 'could reveal mental strength'". Science. Telegraph.co.uk. Archived from the original on 31 May 2008. Retrieved 21 August 2008.
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UpToDate Contents
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- 1. 成人における単極性うつ病：疫学、病因、および神経生物学 unipolar depression in adults epidemiology pathogenesis and neurobiology
- 2. 肥満の病因 pathogenesis of obesity
- 3. 小児および思春期における不安障害：疫学、病因、臨床症状、および経過 anxiety disorders in children and adolescents epidemiology pathogenesis clinical manifestations and course
- 4. 慢性疼痛の定義および病因 definition and pathogenesis of chronic pain
- 5. 気道の神経制御 neuronal control of the airways
English Journal
- Delayed neuroprotection against cerebral ischemia reperfusion injury: putative role of BDNF and GSK-3β.
- Taliyan R1, Ramagiri S1.
- Journal of receptor and signal transduction research.J Recept Signal Transduct Res.2016 Aug;36(4):402-10. doi: 10.3109/10799893.2015.1108338. Epub 2015 Nov 10.
- AIM: Numerous studies have demonstrated the possible neuroprotective role of lithium treatment against neurological disorders. However, the role of lithium in delayed phase of neuronal death against focal ischemia has not been explored. Therefore, the present study was designed to investigate the ef
- PMID 26554621
- Ultrasound of alternating frequencies and variable emotional impact evokes depressive syndrome in mice and rats.
- Morozova A1, Zubkov E1, Strekalova T2, Kekelidze Z3, Storozeva Z3, Schroeter CA4, Bazhenova N5, Lesch KP6, Cline BH7, Chekhonin V8.
- Progress in neuro-psychopharmacology & biological psychiatry.Prog Neuropsychopharmacol Biol Psychiatry.2016 Jul 4;68:52-63. doi: 10.1016/j.pnpbp.2016.03.003. Epub 2016 Mar 29.
- Emotional stress is primarily triggered by the cognitive processing of negative input; it is regarded as a serious pathogenetic factor of depression that is challenging to model in animals. While available stress paradigms achieve considerable face and construct validity in modelling depressive diso
- PMID 27036099
- Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele.
- Cao B1, Bauer IE2, Sharma AN2, Mwangi B2, Frazier T3, Lavagnino L2, Zunta-Soares GB2, Walss-Bass C2, Glahn DC4, Kapczinski F5, Nielsen DA6, Soares JC2.
- Journal of affective disorders.J Affect Disord.2016 Jul 1;198:198-205. doi: 10.1016/j.jad.2016.03.044. Epub 2016 Mar 10.
- BACKGROUND: Previous studies investigated the impact of brain-derived neurotrophic factor (BDNF) val66met (rs6265) on hippocampus volumes and neurocognition in bipolar disorders (BD), but the results were not consistent. This study aimed to investigate the effect of BDNF polymorphism on hippocampus
- PMID 27018938
Japanese Journal
- Impact of Exercise and Vitamin B₁ Intake on Hippocampal Brain-Derived Neurotrophic Factor and Spatial Memory Performance in a Rat Model of Stress
- DIEF Abeer E.,SAMY Diaa M.,DOWEDAR Fatma I.
- Journal of nutritional science and vitaminology 61(1), 1-7, 2015-02
- NAID 40020377912
- Antidepressant-like effect of essential oil isolated from Toona ciliata Roem. var. yunnanensis
- Duan Dongmei,Chen Liping,Yang Xiuyan [他]
- Journal of natural medicines 69(2), 191-197, 2015
- NAID 40020405839
- 高強度インターバルトレーニングと血清脳由来神経栄養因子（BDNF）濃度との関連
- 東 宏一郎,大澤 祐介,田畑 尚吾 [他],堀澤 栞里,勝川 史憲,石田 浩之,小熊 祐子,河合 俊英,小口 修司,太田 敦美,菊池 春人,村田 満,松本 秀男
- 体力科学 64(2), 227-232, 2015
- … To evaluate the association of serum BDNF concentration with high-intensity interval training, 12 healthy male volunteers, aged 28-48 years, completed 16-week high-intensity interval training (HIIT) using ergometer. … However, there was no change in serum BDNF concentration by HIIT. … On the other hand, there was a positive association of serum BDNF concentration at baseline with % increase in peak watt after the intervention (ρ=0.60, p<0.05). …
- NAID 130005063349
Related Links
- この発表資料を分かりやすく解説した「60秒でわかるプレスリリース」もぜひご覧ください。 脳を構成する神経細胞には、小型（直径約50nm）のシナプス小胞※4 と大型（直径約80～120nm）の有芯小胞という2つの袋状の構造をした ...
- →NGF/BDNF/GDNF （→PDGF） 胎生期の神経系の発生や生後のニューロンの維持は、神経栄養因子が担っている。 神経損傷後に起こる再生にも、神経栄養因子が影響を及ぼしている。
Related Pictures
★リンクテーブル★
| リンク元 | 「脳由来神経栄養因子」 |
| 拡張検索 | 「BDNF receptor」「BDNF受容体」「BDNFレセプター」 |