Brain-derived neurotrophic factor

Brain-derived neurotrophic factor

PDB rendering based on 1bnd.
Identifiers
Symbols BDNF; MGC34632
External IDs OMIM: 113505 MGI: 88145 HomoloGene: 7245 GeneCards: BDNF Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 627 12064
Ensembl ENSG00000176697 ENSMUSG00000048482
UniProt P23560 Q541P3
RefSeq (mRNA) NM_001143805.1 NM_001048139
RefSeq (protein) NP_001137277.1 NP_001041604
Location (UCSC) Chr 11:
27.68 – 27.74 Mb		 Chr 2:
109.51 – 109.57 Mb
PubMed search [1] [2]

Brain-derived neurotrophic factor, also known as BDNF, is a secreted protein[1] that, in humans, is encoded by the BDNF gene.[2][3] 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.

Contents

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.[4][5] In the brain, it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking.[6] BDNF itself is important for long-term memory.[7] BDNF was the second neurotrophic factor to be characterized after nerve growth factor (NGF).

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.[8][9][10] 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.[11]

Tissue distribution

Despite its name, 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. BDNF is present in high concentration in hippocampus and cerebral cortex. BDNF is also found in human saliva.[12]

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).[13] It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor.[14]

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").[13]

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. 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.

Secretion

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.[15]

Exercise has been shown to increase the secretion of BDNF at the mRNA and protein levels in the rodent hippocampus, suggesting the potential increase of this neurotrophin after exercise in humans.[16]

Caffeine improves recognition memory, and this effect may be related to an increase of the BDNF and TrkB immunocontent in the hippocampus. [17]

Genetics

The BDNF protein is coded by the gene that is also called BDNF. In humans this gene is located on chromosome 11.[2][3] 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.[18][19]

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.

The polymorphism Thr2Ile may be linked to congenital central hypoventilation syndrome.[20][21]

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).[22][23]

Disease linkage

See also: Neuroplasticity and Medulla oblongata

Various studies have shown possible links between BDNF and conditions, such as depression,[24][25] schizophrenia,[26] obsessive-compulsive disorder,[27] Alzheimer's disease,[28] Huntington's disease,[29] Rett syndrome,[30] and dementia,[31] as well as anorexia nervosa[32] and bulimia nervosa.[33]

Short bouts of excercise can produce an increase in serum BDNF which is hypothesized to be cancelled by exposure to air pollution.[34]

Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when expressed in the ventral tegmental area in rats.[35]

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.[36] 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,[37] caloric restriction, intellectual stimulation, curcumin[38] and various treatments for depression (such as antidepressants[39] and electroconvulsive therapy[40] and sleep deprivation[41]) increase expression of BDNF in the brain. In the case of some treatments such as drugs[42] and electroconvulsive therapy[43] this has been shown to protect or reverse this atrophy.[42]

Eczema

High levels of BDNF and Substance P have been found associated with increased itching in eczema.[44]

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.[45] BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor-mediated post-synaptic currents.[46] 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.[47]

Drug Addiction

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.[48]

Interactions

Brain-derived neurotrophic factor has been shown to interact with TrkB.[49][50] BDNF has also been shown to interact with the reelin signaling chain.[51]The expression of reelin by Cajal-Retzius cells goes down during development under the influence of BDNF.[52] The latter also decreases reelin expression in neuronal culture.

References

  1. ^ Binder DK, Scharfman HE (September 2004). "Brain-derived Neurotrophic Factor". Growth Factors 22 (3): 123–31. doi:10.1080/08977190410001723308. PMC 2504526. PMID 15518235. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2504526. 
  2. ^ 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. http://www.pnas.org/content/87/20/8060. 
  3. ^ a b Maisonpierre PC, Le Beau MM, Espinosa R 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. 
  4. ^ 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. doi:10.1038/374450a0. PMID 7700353. 
  5. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2758233. 
  6. ^ 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. 
  7. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 105 (7): 2711–6. doi:10.1073/pnas.0711863105. PMC 2268201. PMID 18263738. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2268201. 
  8. ^ 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. 
  9. ^ 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. http://www.jneurosci.org/cgi/content/abstract/21/17/6718. 
  10. ^ 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. http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11517260. 
  11. ^ 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. http://www.intjdevbiol.com/paper.php?doi=8645564. 
  12. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2716651. 
  13. ^ a b 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. 
  14. ^ 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. 
  15. ^ MGI database: phenotypes for BDNF homozygous null mice. http://www.informatics.jax.org/searches/allele_report.cgi?_Marker_key=537&int:_Set_key=847156
  16. ^ Cotman CW, Berchtold NC (June 2002). "Exercise: a behavioral intervention to enhance brain health and plasticity". Trends Neurosci. 25 (6): 295–301. doi:10.1016/S0166-2236(02)02143-4. PMID 12086747. http://linkinghub.elsevier.com/retrieve/pii/S0166223602021434. 
  17. ^ http://www.ncbi.nlm.nih.gov/pubmed/18620014
  18. ^ 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. doi:10.1016/S0092-8674(03)00035-7. PMID 12553913. 
  19. ^ 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. http://cabn.psychonomic-journals.org/content/6/1/79.abstract. 
  20. ^ Omim - Brain-Derived Neurotrophic Factor; Bdnf
  21. ^ 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. 
  22. ^ Thorleifsson G, Walters GB, Gudbjartsson DF 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. 
  23. ^ Willer CJ, Speliotes EK, Loos RJ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2695662. 
  24. ^ Dwivedi Y (2009). "Brain-derived neurotrophic factor: role in depression and suicide". Neuropsychiatr Dis Treat 5: 433–49. PMC 2732010. PMID 19721723. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2732010. 
  25. ^ Brunoni, R.; Lopes, M.; Fregni, F. (Dec 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.  edit
  26. ^ Xiu MH, Hui L, Dang YF, De Hou T, Zhang CX, Zheng YL, Chen DC, Kosten TR, Zhang XY (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. 
  27. ^ 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. 
  28. ^ 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. 
  29. ^ Zajac MS, Pang TY, Wong N, Weinrich B, Leang LS, Craig JM, Saffery R, Hannan AJ (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. 
  30. ^ 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. doi:10.1212/01.wnl.0000345664.72220.6a. PMC 2677489. PMID 19349604. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2677489. 
  31. ^ 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. 
  32. ^ 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. doi:10.1159/000120623. PMID 18337636. 
  33. ^ 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. 
  34. ^ I Bos, L. Jacobs, T.S. Nawrot, B. de Geus, R. Torfs, L. Int Panis, B. Degraeuwe, R. Meeusen (August 2011). "No exercise-induced increase in serum BDNF after cycling near a major traffic road.". Neuroscience Letters 500 (2): 129-132. 
  35. ^ Varga-Perez H, Ting-A Kee R, Walton C 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2913611. 
  36. ^ 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. 
  37. ^ 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. 
  38. ^ Xu, Y.; Ku, B.; Tie, L.; Yao, H.; Jiang, W.; Ma, X.; Li, X. (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.  edit
  39. ^ Shimizu, E; Hashimoto, K; Okamura, N; Koike, K; Komatsu, N; Kumakiri, C; Nakazato, M; Watanabe, H 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. 
  40. ^ Okamoto T, Yoshimura R, Ikenouchi-Sugita A, Hori H, Umene-Nakano W, Inoue Y, Ueda N, Nakamura J. (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. 
  41. ^ Gorgulu Y, Caliyurt O (September 2009). "Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression". Brain research bulletin 80 (3): 158–62. doi:10.1016/j.brainresbull.2009.06.016. PMID 19576267. 
  42. ^ a b Drzyzga ŁUkasz R., 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. 
  43. ^ 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. 
  44. ^ "'Blood chemicals link' to eczema". BBC News. 2007-08-26. http://news.bbc.co.uk/2/hi/health/6962450.stm. 
  45. ^ 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. 
  46. ^ 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. http://www.jneurosci.org/cgi/content/abstract/17/9/2959. 
  47. ^ Mattson, M. P. (Nov 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2614307.  edit
  48. ^ Hector Vargas-Perez, Ryan Ting-A-Kee, Christine H. Walton, D. Micah Hansen, Rozita Razavi, Laura Clarke, Mary Rose Bufalino, David W. Allison, Scott C. Steffensen, Derek van der Kooy (2009). "Ventral Tegmental Area BDNF Induces an Opiate-Dependent–Like Reward State in Naïve Rats.". Science. doi:10.1126/science.1168501. PMID 2913611. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913611/. 
  49. ^ Haniu, M; Montestruque S, Bures E J, Talvenheimo J, Toso R, Lewis-Sandy S, Welcher A A, Rohde M F (Oct. 1997). "Interactions between brain-derived neurotrophic factor and the TRKB receptor. Identification of two ligand binding domains in soluble TRKB by affinity separation and chemical cross-linking". J. Biol. Chem. (UNITED STATES) 272 (40): 25296–303. doi:10.1074/jbc.272.40.25296. ISSN 0021-9258. PMID 9312147. 
  50. ^ Naylor, Ruth L; Robertson Alan G S, Allen Shelley J, Sessions Richard B, Clarke Anthony R, Mason Grant G F, Burston Judy J, Tyler Sue J, Wilcock Gordon K, Dawbarn David (Mar. 2002). "A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4". Biochem. Biophys. Res. Commun. (United States) 291 (3): 501–7. doi:10.1006/bbrc.2002.6468. ISSN 0006-291X. PMID 11855816. 
  51. ^ 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. http://www.springer.com/biomed/neuroscience/book/978-0-387-76760-4. ; see the chapter "A Tale of Two Genes: Reelin and BDNF"; pp. 237-245
  52. ^ 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. doi:10.1016/S0896-6273(00)80540-1. PMID 9728912. http://linkinghub.elsevier.com/retrieve/pii/S0896-6273(00)80540-1. 

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