Genomes and Genes
Summary: A protein-tyrosine kinase receptor that is specific for BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN 3; neurotrophin 4 and neurotrophin 5. It is widely expressed in nervous tissue and plays a role in mediating the effects of neurotrophins on growth and differentiation of neuronal cells.
- Jang S, Liu X, Yepes M, Shepherd K, Miller G, Liu Y, et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci U S A. 2010;107:2687-92 pubmed publisher..Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases. ..
- Graham D, Edwards S, Bachtell R, DiLeone R, Rios M, Self D. Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse. Nat Neurosci. 2007;10:1029-37 pubmed..These findings suggest that dynamic induction and release of BDNF from NAc neurons during cocaine use promotes the development and persistence of addictive behavior. ..
- Bernard P, Macdonald D, Gill D, Ryan C, Tasker R. Hippocampal mossy fiber sprouting and elevated trkB receptor expression following systemic administration of low dose domoic acid during neonatal development. Hippocampus. 2007;17:1121-33 pubmed..we report further hippocampal changes, consisting of mossy fiber sprouting and associated changes in the trkB receptor population in young adult (3 months) rats, and further, report that these changes show regional variation ..
- Cameron H, Foster W. Dieldrin promotes resistance to anoikis in breast cancer cells in vitro. Reprod Toxicol. 2008;25:256-62 pubmed publisher..Our results demonstrate that dieldrin increases resistance to anoikis and expression of TrkB and show for the first time TrkB protein expression in human breast cancer. ..
- Donovan M, Yamaguchi M, Eisch A. Dynamic expression of TrkB receptor protein on proliferating and maturing cells in the adult mouse dentate gyrus. Hippocampus. 2008;18:435-9 pubmed publisher..Furthermore, these findings lay critical groundwork for further exploration of the role of BDNF-TrkB signaling in regulation of adult hippocampal neurogenesis. ..
- Yu X, Liu L, Cai B, He Y, Wan X. Suppression of anoikis by the neurotrophic receptor TrkB in human ovarian cancer. Cancer Sci. 2008;99:543-52 pubmed publisher..Adhesive cells showed higher chemosensitivity and lower invasion ability than anoikis-survived cells. Our study suggests that TrkB might mediate anoikis suppression by activating the PI3K-AKT pathway in ovarian cancer cells. ..
- Gruber H, Ingram J, Hoelscher G, Zinchenko N, Norton H, Hanley E. Brain-derived neurotrophic factor and its receptor in the human and the sand rat intervertebral disc. Arthritis Res Ther. 2008;10:R82 pubmed publisher..Our findings point to the need for further studies to define the role of BDNF in the human IVD and to investigate regulatory events within the disc that control the expression of BDNF and its receptor. ..
- Jang S, Liu X, Chan C, Weinshenker D, Hall R, Xiao G, et al. Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity. Chem Biol. 2009;16:644-56 pubmed publisher..Amitriptyline binds the extracellular domain of both TrkA and TrkB and promotes TrkA-TrkB receptor heterodimerization...
- De Santi L, Annunziata P, Sessa E, Bramanti P. Brain-derived neurotrophic factor and TrkB receptor in experimental autoimmune encephalomyelitis and multiple sclerosis. J Neurol Sci. 2009;287:17-26 pubmed publisher..Here we will review the main aspects of BDNF and TrkB receptor involvement in neuroprotective autoimmunity in both EAE and MS...
- Lee T, Saruta J, Sasaguri K, Sato S, Tsukinoki K. Allowing animals to bite reverses the effects of immobilization stress on hippocampal neurotrophin expression. Brain Res. 2008;1195:43-9 pubmed publisher..These findings suggest that biting influences the alterations in neurotrophin levels induced by acute immobilization stress in rat hippocampus. ..
- Li Z, Thiele C. Targeting Akt to increase the sensitivity of neuroblastoma to chemotherapy: lessons learned from the brain-derived neurotrophic factor/TrkB signal transduction pathway. Expert Opin Ther Targets. 2007;11:1611-21 pubmed..Several classes of Akt inhibitors, including phosphatidylinositol ether lipid analogs, alkylphospholipid analogs, allosteric Akt kinase inhibitors, HSP90 inhibitor and HIV protease inhibitors are discussed. ..
- Pillai A, Mahadik S. Increased truncated TrkB receptor expression and decreased BDNF/TrkB signaling in the frontal cortex of reeler mouse model of schizophrenia. Schizophr Res. 2008;100:325-33 pubmed publisher..BDNF, TrkB receptor isoforms (full-length and truncated), reelin, GAD67, GAD65, p75NTR, and NRH-2 levels were measured in the ..
- Miletic G, Miletic V. Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn. Pain. 2008;137:532-9 pubmed..The increased neuronal excitability may in turn have caused enhanced and exaggerated communication between primary afferents and dorsal horn neurons to contribute to the early behavioral signs of pain. ..
- Geiger T, Peeper D. Critical role for TrkB kinase function in anoikis suppression, tumorigenesis, and metastasis. Cancer Res. 2007;67:6221-9 pubmed..Thus, TrkB can act tumorigenically independent of its adhesion motifs. These results suggest that targeting the enzymatic activity of TrkB might be beneficial in cancer therapy. ..
- Liu X, Grishanin R, Tolwani R, RENTERIA R, Xu B, Reichardt L, et al. Brain-derived neurotrophic factor and TrkB modulate visual experience-dependent refinement of neuronal pathways in retina. J Neurosci. 2007;27:7256-67 pubmed..These experiments reveal a previously unrecognized action of BDNF and TrkB in controlling cell-specific, experience-dependent remodeling of neuronal structures in the visual system. ..
- Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C, et al. BDNF as a pain modulator. Prog Neurobiol. 2008;85:297-317 pubmed publisher..Recent studies have unraveled some of the neuronal circuitries and mechanisms involved, highlighting the key role of synaptic glomeruli in lamina II as the main sites for such a modulation. ..
- Kotulska K, Larysz Brysz M, Marcol W, Grajkowska W, Jozwiak S, Lewin Kowalik J. The role of trkB receptor in the formation of post-traumatic neuroma. Folia Neuropathol. 2006;44:221-7 pubmed..We also noticed many more mast cells accumulated at the surgery site in trkB-deficient than in wild-type animals. These results indicate the important role of BDNF receptor in post-traumatic neuroma formation...
- Arancibia S, Silhol M, Mouliere F, Meffre J, Hollinger I, Maurice T, et al. Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats. Neurobiol Dis. 2008;31:316-26 pubmed publisher..These effects involved TrkB receptor activation since they were inhibited by K252a. Catalytic BDNF receptors (TrkB...
- Zhang Z, Han L, Liu Y, Liang X, Sun W. Up-regulation of Tropomyosin related kinase B contributes to resistance to detachment-induced apoptosis in hepatoma multicellular aggregations. Mol Biol Rep. 2009;36:1211-6 pubmed publisher..These data demonstrate that TrkB may contribute to metastasis by facilitating formation of multicellular aggregations and induce their resistance to detachment-induced apoptosis. ..
- Alonso P, Gratacos M, Menchon J, Saiz Ruiz J, Segalas C, Baca Garcia E, et al. Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder. Biol Psychiatry. 2008;63:619-28 pubmed..76; 95% CI = .66-.87; permutation p value = .001). These findings support a role for the BDNF/NTRK2 signaling pathway in genetic susceptibility to OCD. ..
- Kraemer R, Baker P, Kent K, Ye Y, Han J, Tejada R, et al. Decreased neurotrophin TrkB receptor expression reduces lesion size in the apolipoprotein E-null mutant mouse. Circulation. 2005;112:3644-53 pubmed..These data demonstrate, for the first time, a role for the neurotrophin TrkB receptor in atherosclerotic lesion development.
- Von Bohlen Und Halbach O, Krause S, Medina D, Sciarretta C, Minichiello L, Unsicker K. Regional- and age-dependent reduction in trkB receptor expression in the hippocampus is associated with altered spine morphologies. Biol Psychiatry. 2006;59:793-800 pubmed..TrkB functions in structural remodeling of hippocampal dendritic spines, which in turn may affect synaptic transmission and plasticity. ..
- Ricci A, Graziano P, Mariotta S, Cardillo G, Sposato B, Terzano C, et al. Neurotrophin system expression in human pulmonary carcinoid tumors. Growth Factors. 2005;23:303-12 pubmed..TC carcinoids express high affinity NT receptors while 50% of the AC carcinoids express the TrkB receptor. Our results demonstrate that NGF/TrkA and BDNF/TrkB signaling need to be considered as regulatory pathways ..
- Tsukinoki K, Saruta J, Sasaguri K, Miyoshi Y, Jinbu Y, Kusama M, et al. Immobilization stress induces BDNF in rat submandibular glands. J Dent Res. 2006;85:844-8 pubmed..Rat submandibular gland was thus identified as an organ which expresses BDNF. Furthermore, the results of this study suggest that increased salivary BDNF expression occurs following immobilization stress. ..
- Renn C, Lin L, Thomas S, Dorsey S. Full-length tropomyosin-related kinase B expression in the brainstem in response to persistent inflammatory pain. Neuroreport. 2006;17:1175-9 pubmed..These results demonstrate a temporal increase in the number of cells expressing trkB in response to persistent inflammation, suggesting a role for trkB signaling in activity-dependent plasticity in the pain modulatory circuitry. ..
- Miyamoto Y, Yamauchi J, Tanoue A, Wu C, Mobley W. TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology. Proc Natl Acad Sci U S A. 2006;103:10444-10449 pubmed publisher..The findings are evidence of a previously uncharacterized mechanism for the activation of Tiam1 and of a role for this effector in neurotrophin-mediated signal transduction leading to changes in cellular morphology. ..
- Gines S, Bosch M, Marco S, Gavalda N, Diaz Hernandez M, Lucas J, et al. Reduced expression of the TrkB receptor in Huntington's disease mouse models and in human brain. Eur J Neurosci. 2006;23:649-58 pubmed..Therefore, taken together our findings identify TrkB as an additional component that potentially might contribute to the altered neurotrophic support in HD. ..
- Ohira K, Homma K, Hirai H, Nakamura S, Hayashi M. TrkB-T1 regulates the RhoA signaling and actin cytoskeleton in glioma cells. Biochem Biophys Res Commun. 2006;342:867-74 pubmedRecently, the truncated TrkB receptor, T1, has been reported to be involved in the control of cell morphology via the regulation of Rho proteins, through which T1 binds Rho guanine nucleotide dissociation inhibitor (Rho GDI) 1 and ..
- Chhatwal J, Stanek Rattiner L, Davis M, Ressler K. Amygdala BDNF signaling is required for consolidation but not encoding of extinction. Nat Neurosci. 2006;9:870-2 pubmed..Whereas TrkB.t1-infected rats showed normal within-session extinction, their retention of extinction was impaired, suggesting that amygdala TrkB activation is required for the consolidation of stable extinction memories. ..
- Berghuis P, Dobszay M, Wang X, Spano S, Ledda F, Sousa K, et al. Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci U S A. 2005;102:19115-20 pubmed..We find that Src kinase-dependent TrkB receptor transactivation mediates endocannabinoid (eCB)-induced chemotaxis in the absence of BDNF...
- Guo W, Robbins M, Wei F, Zou S, Dubner R, Ren K. Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J Neurosci. 2006;26:126-37 pubmed..Our findings also caution that application of BDNF for recovery from CNS disorders could lead to undesirable central pain. ..
- Qian M, Zhang J, Tan X, Wood A, Gill D, Cho S. Novel agonist monoclonal antibodies activate TrkB receptors and demonstrate potent neurotrophic activities. J Neurosci. 2006;26:9394-403 pubmed..Therefore, they could represent novel reagents to explore the pathophysiological roles of TrkB and its potential therapeutic utility in treating CNS disorders. ..
- Kramer I, Sigrist M, de Nooij J, Taniuchi I, Jessell T, Arber S. A role for Runx transcription factor signaling in dorsal root ganglion sensory neuron diversification. Neuron. 2006;49:379-93 pubmed..Together, our findings suggest that Runx transcription factor signaling plays a key role in sensory neuron diversification. ..
- Islam O, Loo T, Heese K. Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling pathways. Curr Neurovasc Res. 2009;6:42-53 pubmed
- Yang J, Siao C, Nagappan G, Marinic T, Jing D, McGrath K, et al. Neuronal release of proBDNF. Nat Neurosci. 2009;12:113-5 pubmed publisher..Thus, BDNF actions are developmentally regulated by secretion of proBDNF or mature BDNF and by local expression of p75 and TrkB. ..
- ..Li et al. in this issue of Neuron demonstrate that the presence of TrkB, the high-affinity receptor for BDNF, in hippocampal neural progenitor cells is required for the neurogenic and behavioral actions of antidepressant treatments. ..
- Rohe M, Synowitz M, Glass R, Paul S, Nykjaer A, Willnow T. Brain-derived neurotrophic factor reduces amyloidogenic processing through control of SORLA gene expression. J Neurosci. 2009;29:15472-8 pubmed publisher..These findings demonstrate that the beneficial effects ascribed to BDNF in APP metabolism act through induction of Sorla that encodes a negative regulator of neuronal APP processing. ..
- Kawamura K, Kawamura N, Fukuda J, Kumagai J, Hsueh A, Tanaka T. Regulation of preimplantation embryo development by brain-derived neurotrophic factor. Dev Biol. 2007;311:147-58 pubmed..Our findings suggested that BDNF signaling plays important paracrine roles during blastocyst development by promoting the development of preimplantation embryos. ..
- Johansson J, Formaggio E, Fumagalli G, Chiamulera C. Choline up-regulates BDNF and down-regulates TrkB neurotrophin receptor in rat cortical cell culture. Neuroreport. 2009;20:828-32 pubmed publisher..It is speculated that a choline-induced change of alpha7 nAChRs activity may have resulted in the observed increase of BDNF level and down-regulation of the TrkB receptor.
- Vondran M, Clinton Luke P, Honeywell J, Dreyfus C. BDNF+/- mice exhibit deficits in oligodendrocyte lineage cells of the basal forebrain. Glia. 2010;58:848-56 pubmed publisherPrevious work indicated that brain-derived neurotrophic factor (BDNF), through the trkB receptor, increases DNA synthesis in oligodendrocyte (OLG) progenitor cells (OPCs) and differentiation of postmitotic OLGs of the basal forebrain (BF)..
- Wang Z, Mao M, Zhou H, Li S, Yu D. [Signaling pathway of BDNF protecting embryonic cortical neurons from hypoxia]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2007;38:934-7 pubmed..The Ras-MAPK approach may be the major signal transferring way of BDNF in protecting the cortical neurons from hypoxia-induced neurotoxicity. The approach of signal transferring begins with tyrosine phosphorylation of TrkB receptors. ..
- Wang J, Chen B, Yin J, Wang G, Zou W, Luo X. [Effect of electroacupuncture of different acupoints on the excitability of detrusor muscle and the expression of BDNF and TrkB in the spinal cord of rats with urinary retention due to spinal cord injury]. Zhen Ci Yan Jiu. 2009;34:387-92 pubmed
- Krikov M, Thone Reineke C, Muller S, Villringer A, Unger T. Candesartan but not ramipril pretreatment improves outcome after stroke and stimulates neurotrophin BNDF/TrkB system in rats. J Hypertens. 2008;26:544-52 pubmed publisher..Ramipril at sub-hypotensive and hypotensive, RAS-blocking doses showed no significant neuroprotective effects. ..
- Wang C, Bomberg E, Levine A, Billington C, Kotz C. Brain-derived neurotrophic factor in the ventromedial nucleus of the hypothalamus reduces energy intake. Am J Physiol Regul Integr Comp Physiol. 2007;293:R1037-45 pubmed..In summary, BDNF in the VMH significantly decreases food intake and body weight gain, by TrkB receptor-mediated actions. Furthermore, the anorectic effects of BDNF in this site appear to be mediated by NPY...
- Asai N, Abe T, Saito T, Sato H, Ishiguro S, Nishida K. Temporal and spatial differences in expression of TrkB isoforms in rat retina during constant light exposure. Exp Eye Res. 2007;85:346-55 pubmed..These results suggest that BDNF transduces the signals using appropriate receptor isoforms that are expressed temporally and spatially differentially on Mueller cells during light-induced retinal degeneration. ..
- Chiaramello S, Dalmasso G, Bezin L, Marcel D, Jourdan F, Peretto P, et al. BDNF/ TrkB interaction regulates migration of SVZ precursor cells via PI3-K and MAP-K signalling pathways. Eur J Neurosci. 2007;26:1780-90 pubmed..This study identifies a function of BDNF in the SVZ system, which involves multiple protein kinase pathways leading to neuroblast migration. ..
- Carvalho A, Caldeira M, Santos S, Duarte C. Role of the brain-derived neurotrophic factor at glutamatergic synapses. Br J Pharmacol. 2008;153 Suppl 1:S310-24 pubmed..This review focuses on recent advances in the understanding of the regulation of the glutamatergic synapse by BDNF, and its implications in synaptic plasticity. ..
- Dalton V, Roberts B, Borich S. Brain derived neurotrophic factor and trk B mRNA expression in the brain of a brain stem-spinal cord regenerating model, the European eel, after spinal cord injury. Neurosci Lett. 2009;461:275-9 pubmed publisher..Our results are in contrast with the increase reported in mammals but are in line with studies examining neurotrophin expression during CNS regeneration in other anamniotic vertebrates. ..
- Zhou L, Zhong Y, Ren W, Li Y, Zhang T, Liu X. BDNF induces late-phase LTP of C-fiber evoked field potentials in rat spinal dorsal horn. Exp Neurol. 2008;212:507-14 pubmed publisher..The results suggest that BDNF play a crucial role in protein synthesis-dependent L-LTP in spinal dorsal horn via activation of ERK, p38 MAPK and NF-kappaB signal pathways. ..
- Hennigan A, O Callaghan R, Kelly A. Neurotrophins and their receptors: roles in plasticity, neurodegeneration and neuroprotection. Biochem Soc Trans. 2007;35:424-7 pubmed..Here, we briefly give a broad review of current knowledge of the roles of neurotrophins in the adult brain, including expression of hippocampal plasticity, neurodegeneration and exercise-induced neuroprotection. ..
- Hu Y, Cho S, Goldberg J. Neurotrophic effect of a novel TrkB agonist on retinal ganglion cells. Invest Ophthalmol Vis Sci. 2010;51:1747-54 pubmed publisher..Further studies are needed to elucidate the mechanistic differences between this TrkB agonist and BDNF. ..