Editing Brain-derived neurotrophic factor (section)

== Function ==

BDNF acts on certain [[neuron]]s of the [[central nervous system]] and the [[peripheral nervous system]] expressing [[TrkB]], helping to support survival of existing neurons, and encouraging growth and [[Cellular differentiation|differentiation]] of new neurons and [[synapse]]s.<ref name="pmid7700353">{{cite journal | vauthors = Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM | title = A BDNF autocrine loop in adult sensory neurons prevents cell death | journal = Nature | volume = 374 | issue = 6521 | pages = 450–53 | date = March 1995 | pmid = 7700353 | doi = 10.1038/374450a0 | bibcode = 1995Natur.374..450A | s2cid = 4316241 }}</ref><ref name="pmid11520916">{{cite journal | vauthors = Huang EJ, Reichardt LF | title = Neurotrophins: roles in neuronal development and function | journal = Annual Review of Neuroscience | volume = 24 | pages = 677–736 | year = 2001 | pmid = 11520916 | pmc = 2758233 | doi = 10.1146/annurev.neuro.24.1.677 }}</ref>  In the brain it is active in the [[hippocampus]], [[Cerebral cortex|cortex]], and [[basal forebrain]] {{Ndash}}areas vital to [[learning]], [[memory]], and higher thinking.<ref name="pmid12719654">{{cite journal | vauthors = Yamada K, Nabeshima T | title = Brain-derived neurotrophic factor/TrkB signaling in memory processes | journal = Journal of Pharmacological Sciences | volume = 91 | issue = 4 | pages = 267–70 | date = April 2003 | pmid = 12719654 | doi = 10.1254/jphs.91.267 | doi-access = free }}</ref> BDNF is also expressed in the [[retina]], [[kidney]]s, [[prostate]], [[motor neuron]]s, and [[skeletal muscle]], and is also found in [[saliva]].<ref name="pmid19467646">{{cite journal | vauthors = Mandel AL, Ozdener H, Utermohlen V | title = Identification of pro- and mature brain-derived neurotrophic factor in human saliva | journal = Archives of Oral Biology | volume = 54 | issue = 7 | pages = 689–95 | date = July 2009 | pmid = 19467646 | pmc = 2716651 | doi = 10.1016/j.archoralbio.2009.04.005 }}</ref><ref name="DelezieHandschin2018">{{cite journal | vauthors = Delezie J, Handschin C | title = Endocrine Crosstalk Between Skeletal Muscle and the Brain | journal = Frontiers in Neurology | volume = 9 | pages = 698 | year = 2018 | pmid = 30197620 | pmc = 6117390 | doi = 10.3389/fneur.2018.00698 | doi-access = free }}</ref>

BDNF itself is important for [[long-term memory]].<ref name="pmid18263738">{{cite journal | vauthors = Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH | title = BDNF is essential to promote persistence of long-term memory storage | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 7 | pages = 2711–16 | date = February 2008 | pmid = 18263738 | pmc = 2268201 | doi = 10.1073/pnas.0711863105 | bibcode = 2008PNAS..105.2711B | doi-access = free }}</ref>
Although the vast majority of neurons in the [[mammal]]ian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural [[stem cell]]s in a process known as [[neurogenesis]]. Neurotrophins are proteins that help to stimulate and control neurogenesis, BDNF being one of the most active.<ref name="pmid9675054">{{cite journal | vauthors = Zigova T, Pencea V, Wiegand SJ, Luskin MB | title = Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb | journal = Molecular and Cellular Neurosciences | volume = 11 | issue = 4 | pages = 234–45 | date = July 1998 | pmid = 9675054 | doi = 10.1006/mcne.1998.0684 | s2cid = 35630924 }}</ref><ref name="pmid11517261">{{cite journal | vauthors = Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA | title = Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain | journal = The Journal of Neuroscience | volume = 21 | issue = 17 | pages = 6718–31 | date = September 2001 | pmid = 11517261 | pmc = 6763117 | doi = 10.1523/JNEUROSCI.21-17-06718.2001 }}</ref><ref name="pmid11517260">{{cite journal | vauthors = Pencea V, Bingaman KD, Wiegand SJ, Luskin MB | title = 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 | journal = The Journal of Neuroscience | volume = 21 | issue = 17 | pages = 6706–17 | date = September 2001 | pmid = 11517260 | pmc = 6763082 | doi = 10.1523/JNEUROSCI.21-17-06706.2001 }}</ref>  Mice born without the ability to make BDNF have developmental defects in the brain and [[sensory nervous system]], and usually die soon after birth, suggesting that BDNF plays an important role in normal [[neural development]].<ref name="pmid8645564">{{cite journal | vauthors = Ernfors P, Kucera J, Lee KF, Loring J, Jaenisch R | title = Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice | journal = The International Journal of Developmental Biology | volume = 39 | issue = 5 | pages = 799–807 | date = October 1995 | pmid = 8645564 | url = http://www.intjdevbiol.com/paper.php?doi=8645564 }}</ref> Other important neurotrophins structurally related to BDNF include [[NT-3]], [[NT-4]], and [[Nerve growth factor|NGF]].

BDNF is made in the [[endoplasmic reticulum]] and secreted from [[dense-core vesicle]]s. It binds [[carboxypeptidase E]] (CPE), and disruption of this binding has been proposed to cause the loss of sorting BDNF into dense-core vesicles. The [[phenotype]] for BDNF [[knockout mice]] can be severe, including postnatal lethality. Other traits include sensory neuron losses that affect coordination, balance, hearing, taste, and breathing. Knockout mice also exhibit cerebellar abnormalities and an increase in the number of sympathetic neurons.<ref>MGI database: phenotypes for BDNF homozygous null mice. http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537&int:_Set_key=847156</ref>

[[Neurobiological effects of physical exercise|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.<ref name="DelezieHandschin2018"/><ref name="BDNF meta analysis">{{cite journal | vauthors = Szuhany KL, Bugatti M, Otto MW | title = A meta-analytic review of the effects of exercise on brain-derived neurotrophic factor | journal = Journal of Psychiatric Research | volume = 60 | pages = 56–64 | date = January 2015 | pmid = 25455510 | pmc = 4314337 | doi = 10.1016/j.jpsychires.2014.10.003 }}</ref><ref name="epigenome">{{cite journal | vauthors = Denham J, Marques FZ, O'Brien BJ, Charchar FJ | title = Exercise: putting action into our epigenome | journal = Sports Medicine | volume = 44 | issue = 2 | pages = 189–209 | date = February 2014 | pmid = 24163284 | doi = 10.1007/s40279-013-0114-1 | s2cid = 30210091 }}</ref><ref name="trophic factor signaling">{{cite journal | vauthors = Phillips C, Baktir MA, Srivatsan M, Salehi A | title = Neuroprotective effects of physical activity on the brain: a closer look at trophic factor signaling | journal = Frontiers in Cellular Neuroscience | volume = 8 | pages = 170 | year = 2014 | pmid = 24999318 | pmc = 4064707 | doi = 10.3389/fncel.2014.00170 | doi-access = free }}</ref><ref name="Organ response">{{cite journal | vauthors = Heinonen I, Kalliokoski KK, Hannukainen JC, Duncker DJ, Nuutila P, Knuuti J | title = Organ-specific physiological responses to acute physical exercise and long-term training in humans | journal = Physiology | volume = 29 | issue = 6 | pages = 421–36 | date = November 2014 | pmid = 25362636 | doi = 10.1152/physiol.00067.2013 }}</ref> [[Niacin (nutrient)|Niacin]] appears to upregulate BDNF and [[tropomyosin receptor kinase B]] (TrkB) expression as well.<ref name="niacin review 2014">{{cite journal | vauthors = Fu L, Doreswamy V, Prakash R | title = The biochemical pathways of central nervous system neural degeneration in niacin deficiency | journal = Neural Regeneration Research | volume = 9 | issue = 16 | pages = 1509–13 | date = August 2014 | pmid = 25317166 | pmc = 4192966 | doi = 10.4103/1673-5374.139475 | doi-access = free }}</ref>