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==Disease linkage==
==Disease linkage==


Various studies have shown possible links between low levels of BDNF and conditions such as [[clinical depression|depression]],<ref name="pmid19721723">{{cite journal | author = Dwivedi Y | title = Brain-derived neurotrophic factor: role in depression and suicide | journal = Neuropsychiatr Dis Treat | volume = 5 | issue = | pages = 433–49 | year = 2009 | pmid = 19721723 | doi = | url = }}</ref> [[schizophrenia]],<ref name="pmid19720106">{{cite journal | author = Xiu MH, Hui L, Dang YF, De Hou T, Zhang CX, Zheng YL, Chen DC, Kosten TR, Zhang XY | title = Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics | journal = Prog. Neuropsychopharmacol. Biol. Psychiatry | volume = | issue = | pages = | year = 2009 | month = August | pmid = 19720106 | doi = 10.1016/j.pnpbp.2009.08.011 | url = }}</ref> [[obsessive-compulsive disorder]],<ref name="pmid19664825">{{cite journal | author = Maina G, Rosso G, Zanardini R, Bogetto F, Gennarelli M, Bocchio-Chiavetto L | title = Serum levels of brain-derived neurotrophic factor in drug-na?ve obsessive-compulsive patients: A case-control study | journal = J Affect Disord | volume = | issue = | pages = | year = 2009 | month = August | pmid = 19664825 | doi = 10.1016/j.jad.2009.07.009 | url = }}</ref> [[Alzheimer's disease]],<ref name="pmid19498435">{{cite journal | author = Zuccato C, Cattaneo E | title = Brain-derived neurotrophic factor in neurodegenerative diseases | journal = Nat Rev Neurol | volume = 5 | issue = 6 | pages = 311–22 | year = 2009 | month = June | pmid = 19498435 | doi = 10.1038/nrneurol.2009.54 | url = }}</ref> [[Huntington's disease]],<ref name="pmid19499586">{{cite journal | author = Zajac MS, Pang TY, Wong N, Weinrich B, Leang LS, Craig JM, Saffery R, Hannan AJ | title = 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 | journal = Hippocampus | volume = | issue = | pages = | year = 2009 | month = June | pmid = 19499586 | doi = 10.1002/hipo.20658 | url = }}</ref> [[Rett syndrome]],<ref name="pmid19349604">{{cite journal | author = Zeev BB, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E, Vecsler M, Vecksler M, Christodoulou J | title = The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome | journal = Neurology | volume = 72 | issue = 14 | pages = 1242–7 | year = 2009 | month = April | pmid = 19349604 | doi = 10.1212/01.wnl.0000345664.72220.6a | url = }}</ref> and [[dementia]],<ref name="pmid17419049">{{cite journal | author = Arancio O, Chao MV | title = Neurotrophins, synaptic plasticity and dementia | journal = Curr. Opin. Neurobiol. | volume = 17 | issue = 3 | pages = 325–30 | year = 2007 | month = June | pmid = 17419049 | doi = 10.1016/j.conb.2007.03.013 | url = }}</ref> as well as [[anorexia nervosa]]<ref name="pmid18337636">{{cite journal | author = Mercader JM, Fernández-Aranda F, Gratacòs M, Ribasés M, Badía A, Villarejo C, Solano R, González JR, Vallejo J, Estivill X | title = Blood levels of brain-derived neurotrophic factor correlate with several psychopathological symptoms in anorexia nervosa patients | journal = Neuropsychobiology | volume = 56 | issue = 4 | pages = 185–90 | year = 2007 | pmid = 18337636 | doi = 10.1159/000120623 | url = }}</ref> and [[bulimia nervosa]],<ref name="pmid17922530">{{cite journal | author = Kaplan AS, Levitan RD, Yilmaz Z, Davis C, Tharmalingam S, Kennedy JL | title = A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa | journal = Int J Eat Disord | volume = 41 | issue = 1 | pages = 22–8 | year = 2008 | month = January | pmid = 17922530 | doi = 10.1002/eat.20474 | url = }}</ref> though it is still not known whether these levels represent a cause or a symptom.<ref name="pmid17959817">{{cite journal | author = Strand AD, Baquet ZC, Aragaki AK, Holmans P, Yang L, Cleren C, Beal MF, Jones L, Kooperberg C, Olson JM, Jones KR | title = Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration | journal = J. Neurosci. | volume = 27 | issue = 43 | pages = 11758–68 | year = 2007 | month = October | pmid = 17959817 | doi = 10.1523/JNEUROSCI.2461-07.2007 | url = }}</ref><ref name="pmid15655562">{{cite journal | author = Angelucci F, Brenè S, Mathé AA | title = BDNF in schizophrenia, depression and corresponding animal models | journal = Mol. Psychiatry | volume = 10 | issue = 4 | pages = 345–52 | year = 2005 | month = April | pmid = 15655562 | doi = 10.1038/sj.mp.4001637 | url = }}</ref>
Various studies have shown possible links between low levels of BDNF and conditions such as [[clinical depression|depression]], [[schizophrenia]], [[Obsessive-compulsive disorder]], [[Alzheimer's disease]], [[Huntington's disease]], [[Rett syndrome]], and [[dementia]], as well as [[anorexia nervosa]] and [[bulimia nervosa]], though it is still not known whether these levels represent a cause or a symptom.<ref name="pmid17959817">{{cite journal |author=Strand AD, Baquet ZC, Aragaki AK, ''et al.'' |title=Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration |journal=J Neurosci |volume=27 |issue=43 |pages=11758–68 |year=2007 |month=October |pmid=17959817 |doi=10.1523/JNEUROSCI.2461-07.2007 |url=}}</ref><ref>{{cite doi|10.1038/sj.mp.4001637


Increased levels of BDNF can induce a change to an [[Opiate dependency|opiate-dependent-like]] reward state when expressed in the [[ventral tegmental area]] in rats.<ref name="varga">{{cite journal |author=Varga-Perez H, Ting-A Kee R, Walton C, ''et al.'' |title=Ventral Tegmental Area BDNF Induces an Opiate-Dependent-Like Reward State in Naive Rats|journal=Science |volume=324 |issue=5935 |pages=1732-34 |year=2009 |month=June |pmid= |doi=10.1126/science.1168501 |url=}}</ref>
Increased levels of BDNF can induce a change to an [[Opiate dependency|opiate-dependent-like]] reward state when expressed in the [[ventral tegmental area]] in rats.<ref name="varga">{{cite journal |author=Varga-Perez H, Ting-A Kee R, Walton C, ''et al.'' |title=Ventral Tegmental Area BDNF Induces an Opiate-Dependent-Like Reward State in Naive Rats|journal=Science |volume=324 |issue=5935 |pages=1732-34 |year=2009 |month=June |pmid= |doi=10.1126/science.1168501 |url=}}</ref>

Revision as of 17:49, 3 September 2009

Template:PBB Brain-derived neurotrophic factor also known as BDNF is a protein[1] 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.

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.[citation needed]

Mechanism of action

BDNF binds at least two receptors on the surface of cells which 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).[12] It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor.[13]

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 mediates the effects of BDNF and NT-4, TrkA binds and is activated by NGF, and TrkC binds and is activated by NT-3. NT-3 binds to TrkA and TrkB as well, but with less affinity.[12]

The other BDNF receptor, the p75, plays a somewhat less clear role. Some researchers have shown the p75NTR binds and serves as a "sink" for neurotrophins. Cells which 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

BDNF is made in the endoplasmic reticulum and secreted from dense core vesicles. It binds the sorting receptor carboxypeptidase E (CPE) and the disruption of this binding causes loss of sorting of BDNF into dense core vesicles. However, knockout animal studies showed no deficit.

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.[14]

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.[15][16]

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.[17][18]

In 2009 variants close to the BDNF gene were found to associatate with obesity in two very large genome wide association studies of body mass index (BMI).[19][20]

Disease linkage

Various studies have shown possible links between low levels of BDNF and conditions such as depression,[21] schizophrenia,[22] obsessive-compulsive disorder,[23] Alzheimer's disease,[24] Huntington's disease,[25] Rett syndrome,[26] and dementia,[27] as well as anorexia nervosa[28] and bulimia nervosa,[29] though it is still not known whether these levels represent a cause or a symptom.[30][31]

Increased levels of BDNF can induce a change to an opiate-dependent-like reward state when expressed in the ventral tegmental area in rats.[32]

Depression

Exposure to stress and the stress hormone corticosterone has been shown to decrease the expression of BDNF in rats, and leads to an eventual atrophy of the hippocampus if exposure is persistent. Atrophy of the hippocampus and other limbic structures has been shown to take place in humans suffering from chronic depression.[33] In addition, rats bred to be heterozygous for BDNF, therefore reducing its expression, have been observed to exhibit similar hippocampal atrophy, suggesting that an etiological link between the development of depressive illness and regulation of BDNF exists. On the other hand, the excitatory neurotransmitter glutamate, voluntary exercise,[34] caloric restriction, intellectual stimulation, curcumin and various treatments for depression (such as antidepressants and electroconvulsive therapy) strongly increase expression of BDNF in the brain, and have been shown to protect against this atrophy.[citation needed]

Eczema

High levels of BDNF and Substance P have been found associated with increased itching in eczema.[35]

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.[36] BDNF modulates excitatory and inhibitory synaptic transmission by inhibiting GABAA-receptor mediated post-synaptic currents.[37] This provides a potential mechanism for the observed up-regulation.

Interactions

Brain-derived neurotrophic factor has been shown to interact with TrkB.[38][39] BDNF has also been shown to interact with the reelin signaling chain.[40] The expression of reelin by Cajal-Retzius cells goes down during development under the influence of BDNF.[41] The latter also decreases reelin expression in neuronal culture.

References

  1. ^ Binder DK, Scharfman HE (2004). "Brain-derived neurotrophic factor". Growth Factors. 22 (3): 123–31. doi:10.1080/08977190410001723308. PMC 2504526. PMID 15518235. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ a b Jones KR, Reichardt LF (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  3. ^ a b Maisonpierre PC, Le Beau MM, Espinosa R; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM (1995). "A BDNF autocrine loop in adult sensory neurons prevents cell death". Nature. 374 (6521): 450–3. doi:10.1038/374450a0. PMID 7700353. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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. PMID 11520916.
  6. ^ Yamada K, Nabeshima T (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Zigova T, Pencea V, Wiegand SJ, Luskin MB (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA (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. {{cite journal}}: Unknown parameter |day= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (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. {{cite journal}}: Unknown parameter |day= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ Ernfors P, Kucera J, Lee KF, Loring J, Jaenisch R (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ a b Patapoutian A, Reichardt LF (2001). "Trk receptors: mediators of neurotrophin action". Curr. Opin. Neurobiol. 11 (3): 272–80. doi:10.1016/S0959-4388(00)00208-7. PMID 11399424. {{cite journal}}: Unknown parameter |month= ignored (help)
  13. ^ Fernandes CC, Pinto-Duarte A, Ribeiro JA, Sebastião AM (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Cotman CW, Berchtold NC (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  15. ^ Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ Bath KG, Lee FS (2006). "Variant BDNF (Val66Met) impact on brain structure and function" ([dead link] – Scholar search). Cogn Affect Behav Neurosci. 6 (1): 79–85. doi:10.3758/CABN.6.1.79. PMID 16869232. {{cite journal}}: External link in |format= (help); Unknown parameter |month= ignored (help)
  17. ^ Omim - Brain-Derived Neurotrophic Factor; Bdnf
  18. ^ 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: 306–310. doi:10.1002/ajmg.10133. PMID 11840487.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ Thorleifsson G, Walters GB, Gudbjartsson DF; et al. (2009). "Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity". Nat. Genet. 41 (1): 18–24. PMID 19079260. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Willer CJ, Speliotes EK, Loos RJ; et al. (2009). "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation". Nat. Genet. 41 (1): 24–34. PMID 19079261. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  21. ^ Dwivedi Y (2009). "Brain-derived neurotrophic factor: role in depression and suicide". Neuropsychiatr Dis Treat. 5: 433–49. PMID 19721723.
  22. ^ Xiu MH, Hui L, Dang YF, De Hou T, Zhang CX, Zheng YL, Chen DC, Kosten TR, Zhang XY (2009). "Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics". Prog. Neuropsychopharmacol. Biol. Psychiatry. doi:10.1016/j.pnpbp.2009.08.011. PMID 19720106. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Maina G, Rosso G, Zanardini R, Bogetto F, Gennarelli M, Bocchio-Chiavetto L (2009). "Serum levels of brain-derived neurotrophic factor in drug-na?ve obsessive-compulsive patients: A case-control study". J Affect Disord. doi:10.1016/j.jad.2009.07.009. PMID 19664825. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Zuccato C, Cattaneo E (2009). "Brain-derived neurotrophic factor in neurodegenerative diseases". Nat Rev Neurol. 5 (6): 311–22. doi:10.1038/nrneurol.2009.54. PMID 19498435. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ Zajac MS, Pang TY, Wong N, Weinrich B, Leang LS, Craig JM, Saffery R, Hannan AJ (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. doi:10.1002/hipo.20658. PMID 19499586. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  26. ^ Zeev BB, Bebbington A, Ho G, Leonard H, de Klerk N, Gak E, Vecsler M, Vecksler M, Christodoulou J (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. PMID 19349604. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Arancio O, Chao MV (2007). "Neurotrophins, synaptic plasticity and dementia". Curr. Opin. Neurobiol. 17 (3): 325–30. doi:10.1016/j.conb.2007.03.013. PMID 17419049. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  29. ^ Kaplan AS, Levitan RD, Yilmaz Z, Davis C, Tharmalingam S, Kennedy JL (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  30. ^ Strand AD, Baquet ZC, Aragaki AK, Holmans P, Yang L, Cleren C, Beal MF, Jones L, Kooperberg C, Olson JM, Jones KR (2007). "Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration". J. Neurosci. 27 (43): 11758–68. doi:10.1523/JNEUROSCI.2461-07.2007. PMID 17959817. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  31. ^ Angelucci F, Brenè S, Mathé AA (2005). "BDNF in schizophrenia, depression and corresponding animal models". Mol. Psychiatry. 10 (4): 345–52. doi:10.1038/sj.mp.4001637. PMID 15655562. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  32. ^ Varga-Perez H, Ting-A Kee R, Walton C; et al. (2009). "Ventral Tegmental Area BDNF Induces an Opiate-Dependent-Like Reward State in Naive Rats". Science. 324 (5935): 1732–34. doi:10.1126/science.1168501. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  33. ^ 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.
  34. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  35. ^ BBC (2007-08-26). "'Blood chemicals link' to eczema". BBC NEWS.
  36. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  37. ^ Tanaka T, Saito H, Matsuki N (1997). "Inhibition of GABAA synaptic responses by brain-derived neurotrophic factor (BDNF) in rat hippocampus". J. Neurosci. 17 (9): 2959–66. PMID 9096132. {{cite journal}}: Unknown parameter |day= ignored (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  38. ^ Haniu, M (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. 272 (40). UNITED STATES: 25296–303. ISSN 0021-9258. PMID 9312147. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)
  39. ^ Naylor, Ruth L (2002). "A discrete domain of the human TrkB receptor defines the binding sites for BDNF and NT-4". Biochem. Biophys. Res. Commun. 291 (3). United States: 501–7. doi:10.1006/bbrc.2002.6468. ISSN 0006-291X. PMID 11855816. {{cite journal}}: Check date values in: |year= (help); Cite has empty unknown parameters: |laydate=, |laysource=, and |laysummary= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help); Unknown parameter |quotes= ignored (help)
  40. ^ 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
  41. ^ Ringstedt T, Linnarsson S, Wagner J, Lendahl U, Kokaia Z, Arenas E, Ernfors P, Ibáñez CF (1998). "BDNF regulates reelin expression and Cajal-Retzius cell development in the cerebral cortex". Neuron. 21 (2): 305–15. PMID 9728912. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

External links

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