同: BDNF

同: BDNF

WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
obtain; "derive pleasure from ones garden" (同)gain
develop or evolve from a latent or potential state (同)educe
come from; "The present name derives from an older form"
come from; be connected by a relationship of blood, for example; "She was descended from an old Italian noble family"; "he comes from humble origins" (同)come, descend
kill by smashing someones skull
mental ability; "hes got plenty of brains but no common sense" (同)brainpower, learning_ability, mental capacity, mentality, wit
that part of the central nervous system that includes all the higher nervous centers; enclosed within the skull; continuous with the spinal cord (同)encephalon
the brain of certain animals used as meat
hit on the head
formed or developed from something else; not original; "the belief that classes and organizations are secondary and derived"- John Dewey

PrepTutorEJDIC

(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
《『derive』+『名』+『from』+『名』(do『ing』)》(…から)…‘を'『引き出す』,得る,求める / 《『derive from』+『名』(do『ing』)》《文》(…から)派生する,(…に)由来する
『脳』,脳髄 / 《しばしば複数形で》『頭脳』,『知力』 / 《話》秀才,知的指導者 / …‘の'頭を打ち砕く

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/17 21:49:43」(JST)

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Brain-derived neurotrophic factor, also known as BDNF, is a secreted 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", NGF. Neurotrophic factors are found in the brain and the periphery.

Function[edit]

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] BDNF itself is important for long-term memory.^[8] BDNF was the second neurotrophic factor to be characterized after nerve growth factor (NGF).

BDNF is expressed within the dentate gyrus and CA4-2 of the adult human. Allen Brain Atlases

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.^[9]^[10]^[11] 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.^[12]

In addition to its production and functions in the brain and nervous system, BDNF secreted by contracting muscle has been found to play a role in muscle repair, regeneration, and differentiation. This is supplementary to its well-known functions in neurobiology. BDNF can therefore now be identified as a myokine that plays a role in peripheral metabolism, myogenesis, and muscle regeneration.^[13]

Tissue distribution[edit]

Counterintuitively, BDNF is actually found in a range of tissue and cell types, not just in the brain. It is also expressed in the retina, the central nervous system, motor neurons, the kidneys, and the prostate.^{[citation needed]} BDNF is present in high concentration in hippocampus and cerebral cortex. BDNF is also found in human saliva.^[14]

Mechanism of action[edit]

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).^[15] It may also modulate the activity of various neurotransmitter receptors, including the α₇ nicotonic receptor.^[16]

TrkB is a receptor tyrosine kinase (meaning it mediates its actions by causing the addition of phosphate molecules on certain tyrosines in the cell, activating cellular signaling). There are other related Trk receptors, TrkA and TrkC. Also, there are other neurotrophic factors structurally related to BDNF: NGF (for Nerve Growth Factor), NT-3 (for Neurotrophin-3) and NT-4 (for Neurotrophin-4). While TrkB is the primary receptor for BDNF and NT-4, TrkA is the receptor for NGF, and TrkC is the primary receptor for NT-3. NT-3 binds to TrkA and TrkB as well, but with less affinity (thus the caveat "primary receptor").^[15]

The other BDNF receptor, the p75, plays a somewhat less clear role. Some researchers have shown that the p75NTR binds and serves as a "sink" for neurotrophins. Cells that express both the p75NTR and the Trk receptors might, therefore, have a greater activity, since they have a higher "microconcentration" of the neurotrophin.^{[citation needed]} It has also been shown, however, that the p75NTR may signal a cell to die via apoptosis; so, therefore, cells expressing the p75NTR in the absence of Trk receptors may die rather than live in the presence of a neurotrophin.^{[citation needed]}

Secretion[edit]

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]

Exercise has been shown to increase the secretion of BDNF as a myokine at the mRNA and protein levels in the rodent hippocampus, suggesting the potential increase of this neurotrophin after exercise in humans.^[18]^[19] It is well known that BDNF increases in brain tissue in response to acute exercise and exercise training and may account for the effect of exercise in the protection against neurodegenerative diseases such as dementia. Recent studies have thus confirmed that exercise induces an expression of BDNF in skeletal muscle, as well as in the brain.^[13]

Caffeine improves recognition memory, and this effect may be related to an increase of the BDNF and TrkB immunocontent in the hippocampus.^[20]

Effects of physical activity on cognition[edit]

BDNF activity is correlated with increased long term potentiation and neurogenesis, which can be induced by physical activity.^[21] Long term potentiation is shown to improve learning and memory by strengthening the communication between specific neurons. This was shown in the Morris water maze task in which the role of BDNF was tested in mice. One group of mice exercised on a running wheel while the control group of mice trained under standard conditions lacking physical exercise. When the groups of mice performed the Morris water maze task, the running group significantly increased their learning and memory by decreasing the latency in finding the platform.^[21] Bromodeoxyuridine was injected into the mice to label dividing cells which proved to show that the physical exercise enhanced neurogenesis in the dentate gyrus of the hippocampus of the running mice, thus enhancing long term potentiation and memory.^[22]

The increase in neurogenesis is hypothesized to increase learning in the mice.^[22] MRI scans have shown that exercising mice have a selective increase in cerebral blood flow to the dentate gyrus of the hippocampus, an area of the brain particular to memory and learning, while there was no significant increase observed in other areas of the brain. The control mice group with no exercise did not have the same increase in the hippocampal region. This supporting evidence concludes that exercise selectively increases neurogenesis in the dentate gyrus of the hippocampus.^[23]

The mechanism for this is due to BDNF activating the signal transduction cascades, MAP kinase and CAMKII, which regulate the expression of the transcription factor, CREB, and protein synapsin I. The mitochondria and the uncoupling protein, UCP2, which is mainly present in the brain’s mitochondria, have been thought to interact with this signal transduction cascade during physical activity. CREB and synapsin I both play a role in enhancing plasticity by changing the structure of the neuron and strengthening its signaling capability, therefore affecting long term potentiation. CREB specifically aids in spatial learning and regulating gene expression, while synapsin I modulates the release of neurotransmitters and affects the actin cytoskeleton of the cell which enhances the signaling capability of the neuron by changing its shape and density.^[24]

Genetics[edit]

The BDNF protein is coded by the gene that is also called BDNF. In humans this gene is located on chromosome 11.^[3]^[4] 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.^[25]^[26]

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.^{[citation needed]}

The polymorphism Thr2Ile may be linked to congenital central hypoventilation syndrome.^[27]^[28]

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).^[29]^[30]

Disease linkage[edit]

See also: Neuroplasticity and Medulla oblongata

Various studies have shown possible links between BDNF and conditions such as depression,^[31]^[32] bipolar disorder,^[33] schizophrenia,^[34] obsessive-compulsive disorder,^[35] Alzheimer's disease,^[36] Huntington's disease,^[37] Rett syndrome,^[38] and dementia,^[39] as well as anorexia nervosa^[40] and bulimia nervosa.^[41]

Short bouts of exercise can produce an increase in serum BDNF which is hypothesized to be cancelled by exposure to air pollution.^[42] In rodents, BDNF gene expression in the brain may also be down-regulated following exposure to air pollution.^[19]^[43]

Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when expressed in the ventral tegmental area in rats.^[44]

Inclusive results have suggested the possibility of BDNF dysregulation in Autism Spectrum Disorders. ^[45]^[46]^[47]

Depression[edit]

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.^[48] 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,^[49] caloric restriction, intellectual stimulation, curcumin^[50] and various treatments for depression (such as antidepressants^[51] and electroconvulsive therapy^[52] and sleep deprivation^[53]) increase expression of BDNF in the brain. In the case of some treatments such as drugs^[54] and electroconvulsive therapy.^[55] This has been shown to protect or reverse this atrophy.^[54]

Eczema[edit]

High levels of BDNF and Substance P have been found associated with increased itching in eczema.^[56]

Epilepsy[edit]

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.^[57] BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor-mediated post-synaptic currents.^[58] This provides a potential mechanism for the observed up-regulation.

Alzheimer's disease[edit]

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. A connection between depression and dementia has been suggested to be mediated by BDNF. Depression causes shrinkage of the hippocampus. When antidepressants are administered, the levels of BDNF are raised to protect and increase the volume of hippocampal and other cells. In Alzheimer's, the hippocampus is also damaged, lowering levels of the neurotrophic factor.^[59] Another possible link between BDNF and dementia is through fitness, since exercise can release BDNF and preserve cognition in older people.^[60]

Drug Addiction[edit]

BDNF is a critical regulator of drug dependency. 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 dependent on opiates.^[44]

Interactions[edit]

Brain-derived neurotrophic factor has been shown to interact with TrkB.^[61]^[62] BDNF has also been shown to interact with the reelin signaling chain.^[63] The expression of reelin by Cajal-Retzius cells is decreased during development under the influence of BDNF.^[64]

References[edit]

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External links[edit]

Cotman CW, Berchtold NC (2004-01-28). "BDNF and Alzheimer's Disease—What's the Connection?". Alzforum: Live Discussions. Alzheimer Research Forum. Retrieved 2008-08-21.
Patten-Hitt E (2001-06-14). "Brain-Derived Neurotrophic Factor (BDNF)". Sciencexpress. The HDLighthouse, Huntingtons Disease: Information and Community. Retrieved 2008-08-21.
Highfield R (2007-10-18). "Brain scans 'could reveal mental strength'". Science. Telegraph.co.uk. Archived from the original on 2008-05-31. Retrieved 2008-08-21. "Low BDNF activity promotes resilience"

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. 慢性疼痛の定義および病因 definition and pathogenesis of chronic pain
4. ハンチントン病：管理 huntington disease management
5. 成人における単極性うつ病および選択的セロトニン再取り込み阻害剤（SSRIs）：
薬理学、投与方法、および副作用 unipolar depression in adults and selective serotonin reuptake inhibitors ssris pharmacology administration and side effects

English Journal

Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats.

Sallaberry C, Nunes F, Costa MS, Fioreze GT, Ardais AP, Botton PH, Klaudat B, Forte T, Souza DO, Elisabetsky E, Porciúncula LO.SourceLaboratory of Studies on the Purinergic System, Department of Biochemistry, Health and Basic Sciences Institute, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS 90035 003, Brazil; PPG-Neurociências, Health and Basic Sciences Institute, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS 90035 003, Brazil.
Neuropharmacology.Neuropharmacology.2013 Jan;64(1):153-9. doi: 10.1016/j.neuropharm.2012.07.010. Epub 2012 Jul 27.
Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modu
PMID 22841916

Chronic phosphodiesterase type 2 inhibition improves memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

Sierksma AS, Rutten K, Sydlik S, Rostamian S, Steinbusch HW, van den Hove DL, Prickaerts J.SourceDepartment of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Science, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, the Netherlands; European Graduate School of Neuroscience (EURON), Maastricht, The Netherlands.
Neuropharmacology.Neuropharmacology.2013 Jan;64(1):124-36. doi: 10.1016/j.neuropharm.2012.06.048. Epub 2012 Jul 4.
Alzheimer's disease (AD) is characterized by progressive cognitive deficits and synaptic dysfunction. Over the last decade phosphodiesterase inhibitors (PDEIs) have received increasing attention as putative cognition enhancers and have been suggested as a novel treatment strategy for AD. Given their
PMID 22771768

Japanese Journal

中枢によるインスリン感受性制御 : BDNFを中心に (特集ホルモン作用と臓器相関)

須田将吉,林由香,吉田陽子 [他]
内分泌・糖尿病・代謝内科 38(1), 25-32, 2014-01
NAID 40019957579

Baicalin improves chronic corticosterone-induced learning and memory deficits via the enhancement of impaired hippocampal brain-derived neurotrophic factor and cAMP response element-binding protein expression in the rat

Lee Bombi,Sur Bongjun,Shim Insop [他]
Journal of natural medicines 68(1), 132-143, 2014
NAID 40019919857

Effect of Repetitive Transcranial Magnetic Stimulation and Intensive Occupational Therapy on Serum Levels of Brain-derived Neurotrophic Factor in Patients after Stroke (Original)

Naoki Yamada,Masahiro Abo,Masato Shimizu,Wataru Kakuda,Sugao Mitani,Hidenobu Saeki,Takahiro Kondo,Junichi Nishimura,Naomi Nojima
Jikeikai medical journal 60(4), 47-54, 2013-12-10
NAID 120005368850

Related Pictures

★リンクテーブル★

リンク元	「BDNF」「脳由来神経栄養因子」
関連記事	「derive」「fact」「factor」「neurotrophic」「brain」

「BDNF」

Brain-derived neurotrophic factor
	; PDB rendering based on 1bnd.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1B8M, 1BND
Identifiers
Symbols	BDNF; ANON2; BULN2
External IDs	OMIM: 113505 MGI: 88145 HomoloGene: 7245 GeneCards: BDNF Gene
Gene Ontology
Molecular function	• neurotrophin TRKB receptor binding; • growth factor activity;
Cellular component	• extracellular region; • cytoplasm; • synaptic vesicle; • perinuclear region of cytoplasm;
Biological process	• ureteric bud development; • response to hypoxia; • chronic inflammatory response; • mitochondrial electron transport, NADH to ubiquinone; • nervous system development; • negative regulation of neuroblast proliferation; • axon guidance; • axon target recognition; • learning or memory; • feeding behavior; • neuron recognition; • response to hormone stimulus; • glutamate secretion; • response to fluoxetine; • dendrite development; • regulation of metabolic process; • nerve development; • response to vitamin A; • mechanoreceptor differentiation; • fear response; • negative regulation of neuron apoptotic process; • positive regulation of neuron differentiation; • negative regulation of striated muscle tissue development; • regulation of retinal cell programmed cell death; • positive regulation of long-term neuronal synaptic plasticity; • regulation of short-term neuronal synaptic plasticity; • inner ear development; • positive regulation of synapse assembly; • response to hyperoxia; • regulation of excitatory postsynaptic membrane potential; • response to anesthetic;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

日
関

関: Brain-derived neurotrophic factor
同: brain-derived neurotrophic factor

関: Brain-derived neurotrophic factor

「脳由来神経栄養因子」

　　[★]

英: brain-derived neurotrophic factor、BDNF
同: 脳由来神経因子
関: 神経成長因子

「derive」

　　[★]

vt.

由来する

同: stem

由来する、派生する、引き出す

関: borne、come from、descend、draw、educe、elicit、stem

「fact」

　　[★]

n.

事実、現状、実際、実態

関: actual、actually、in fact、in practice、indeed、practically

「factor」

　　[★]

n.

因子、要因、要素、ファクター

関: element、elementary、factorial、parameter

「neurotrophic」

　　[★]

神経栄養の、神経栄養性の

「brain」

　　[★] 脳

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brain-derived neurotrophic factor