Brain Derived Neurotrophic Factor

Year 2015, Volume: 10 Issue: 2, 120 - 129, 20.10.2015

Gül Yarım , Filiz Kazak

https://doi.org/10.17094/avbd.02290

Cited By: 5

Abstract

Brain-derived neurotrophic factor (BDNF), is a member of neurotrophin family having roles in survival, growth and function of neurons in the central and peripheral nervous system. BDNF mRNA and protein levels have been identified in the cerebellum, hippocampus, bulbus olfactorius, spinal cord, thalamus, prefrontal cerebral cortex, hypothalamus, amygdala, regions of the projections of the olfactory system, striatum and superior colliculus. Although the early BDNF expression studies have demonstrated that this molecule were related with neurons, while in subsequent studies the BDNF synthesis have been determined in non-neuronal cells of central nervous system, peripheral vascular endothelial cells, lymphocytes, platelets, leukocytes, monocytes, T and B lymphocytes. Also, BDNF mRNA expression has been reported in heart, lung, kidney, spleen and urinary bladder cells. The expression and concentration of BDNF varies in physiological events and pathological situations. BDNF serves mainly to the development and refreshment of neurons in the central nervous system in addition to contributing to be structurally healthy of important nerve pathways and to the continuity of their performance. Because of the importance of BDNF to the neuronal survival and function in nervous system, applications of this neurotrophin in treatment of neurodegenerative diseases has gained importance and acceleration. The purpose of this review is to provide information about the structure, synthesis, functions and therapeutic use of BDNF.

Keywords

BDNF, Neurodegeneration, p75NTR, TrkB

Beyin Kaynaklı Nörotrofik Faktör

Abstract

Beyin kaynaklı nörotrofik faktör (BDNF), nörotrofin ailesinin bir üyesi olup merkezi ve çevresel sinir sisteminde nöronların yaşamasında, büyümesinde ve fonksiyonlarında görev alır. BDNF mRNA ve protein düzeyleri serebellum, hipokampus, bulbus olfaktorius, medulla spinalis, talamus,  prefrontal serebral korteks, hipotalamus, amigdala, koku sisteminin projeksiyon bölgeleri, striatum ve superior kollikulusta tespit edilmiştir. Yapılan ilk BDNF ekspresyonu çalışmalarında molekülün nöronlarla ilişkili olduğu belirlenmiş olmasına rağmen, daha sonraki çalışmalarda BDNF’nin merkezi sinir sisteminde nöron harici hücrelerden, periferde vasküler endotel hücrelerinden, lenfositlerden, trombositlerden, lökositlerden, monositlerden, T ve B lenfositlerden sentezlendiği belirlenmiştir. Kalp, akciğer, böbrek, dalak ve mesane hücrelerinde de BDNF mRNA ekspresyonu rapor edilmiştir. BDNF ekspresyonu ve konsantrasyonu fizyolojik olaylarda ve patolojik durumlarda değişmektedir. BDNF, merkezi sinir sisteminde esas olarak nöronların gelişmelerine ve kendilerini yenilemelerine yardımcı olurken, önemli sinir yolaklarının yapısal olarak sağlıklı olmalarına ve görevlerini sürdürmelerine de katkıda bulunur. Sinir sisteminde nöronların sağkalımını desteklemesi ve nöronal fonksiyonları etkilemesinden dolayı nörodejeneratif hastalıkların tedavi edilmesinde, BDNF uygulamaları önem ve hız kazanmıştır. Bu derlemenin amacı, BDNF’nin yapısı, sentezi, etki mekanizması,  fonksiyonları ve tedavi amaçlı kullanımı hakkında bilgi vermektir.

Keywords

BDNF, Nörodejenerasyon, p75NTR, TrkB

References

• Alderson RF., Alterman AL., Barde YA, Lindsay RM., 1990. Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron, 5, 297-306.
• Almeida LE., Roby CD., Krueger BK., 2014. Increased BDNF expression in fetal brain in the valproic acid model of autism. Mol. Cell Neurosci., 59C, 57-62.
• Angelucci ngelucci F., Aloe L., Vasquez PJ., Mathe AA., 2000. Mapping the differences in the brain of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in animal model of depression. Neuroreport, 11 (6), 1369-1373.
• Angelucci F., Oliviero A., Pilato F., Saturno E., Dileone M., Versace V., Musumeci G., Batocchi AP., Tonali PA., Di Lazzaro V., 2004. Transcranial magnetic stimulation and BDNF plasma levels in amyotrophic lateral sclerosis. Neuroreport, 15 (4), 717-720.
• Barbacid M., 1994. The Trk family of neurotrophin receptors. J. Neurobiol., 25, 1386-1403.
• Bekinschtein P., Cammarota M., Izquierdo I., Medina JH., 2008. BDNF and Memory Formation and Storage. Neuroscientist, 14 (2), 147-156.
• Blöchl A., Sirrenberg C., 1996. Neurotrophins stimulate the release of dopamine from rat mesencephalic neurons via Trk and p75Lntr receptors. J. Biol. Chem., 271, 21100-21107.
• Bramham CR., Southard T., Sarvey JM., Herkenhem M., Brady LS., 1996. Unilateral LTP triggers bilateral increases in hippocampal neurotrophin and trk receptor mRNA expression in behaving rats: evidence for interhemispheric communication. J. Comp. Neurol., 368 (3), 371-382.
• Castrén E., Thoenen H., Lindholm D., 1995. Brain derived neurotrophic factor messenger RNA is expressed in the septum, hypothalamus and in adrenergic brain stem nuclei of adult rat brain and is increased by osmotic stimulation in the paraventricular nucleus. Neuroscience, 64 (1), 71-80.
• Chao MV., Hempstead BL., 1995. p75 and Trk: a two-receptor system. Trends Neurosci., 18 (7), 321-326.
• Chen B., Dowlatshahi D., MacQueen GM., Wang JF., Young LT., 2001. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol. Psychiatry, 50 (4), 260-265.
• Chou D., Huang CC., Hsu KS., 2014. Brain-derived neurotrophic factor in the amygdala mediates susceptibility to fear conditioning. Exp Neurol., 255, 19-29.
• Cotman CW., Berchtold NC., 2002. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci., 25 (6), 295-301.
• Cunha C., Brambilla R., Thomas KL., 2010. A simple role for BDNF in learning and memory? Front Mol. Neurosci., 3 (1), 1-14.
• Dechant G., Barde YA., 2002. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat. Neurosci., 5, 1131-1136.
• Deinhardt K., Chao MV., 2014. Shaping neurons: Long and short range effects of mature and proBDNF signalling upon neuronal structure. Neuropharmacology, 76, 603-609.
• Dugich-Djordjevic MM., Peterson C., Isono F., Widmer HR., Denton TL., Bennett GL., Hefti F., 1995. Immunohistochemical visualization of brain-derived neurotrophic factor in the rat brain. Eur. J. Neurosci., 7 (9), 1831-1839.
• Eaton MJ., Whittemore SR., 1996. Autocrine BDNF secretion enhances the survival and serotonergic differentiation of raphe neuronal precursor cells grafted into the adult rat CNS. Exp. Neurol., 140, 105-114.
• Faria MC., Gonçalves GS., Rocha NP., Moraes EN., Bicalho MA., Gualberto Cintra MT., Jardim de Paula J., José Ravic de Miranda LF., Clayton de Souza Ferreira A., Teixeira AL., Gomes KB., Carvalho MD., Sousa LP., 2014. Increased plasma levels of BDNF and inflammatory markers in Alzheimer's disease. J. Psychiatr. Res., pii: S0022-3956(14)00028-4. doi: 10.1016/j.jpsychires.2014.01.019.
• Forlenza OV., Diniz BS., Teixeira AL., Ojapi EB., Talib LL., Mendonça VA., Izzo G., Gattaz WF., 2010. Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment. World J. Biol. Psychiatry, 11 (6), 774-780.
• Frota ER., Rodrigues DH., Donadi EA., Brum DG., Maciel DR., Teixeira AL., 2009. Increased plasma levels of brain derived neurotrophic factor (BDNF) after multiple sclerosis relapse. Neurosci. Lett., 460 (2), 130-132.
• Gielen A., Khademi M., Muhallab S., Olsson T., Piehl F., 2003. Increased brain derived neurotrophic factor expression in white blood cells of relapsing- remitting multible sclerosis patients. Scand. J. Immunol., 57 (5), 493-497.
• Heath D., Schmidt MB., Duman RS., 2008. Future Antidepressant Targets: Neurotrophic Factors and Related Signaling Cascades. Drug Discov. Today Ther. Strateg., 5 (3), 151-156.
• Hofer M., Pagliusu SR., Hohn A, Leibrock J., Barok YA., 1990. Regional distrubition of brain derived neurotrophic factor mRNA in the adulth mouse brain. EMBO J., 9 (8), 2459-2464.
• Hohlfeld R., Kerschensteiner M., Stadelmann C., Lassmann H., Wekerle H., 2000. The neuroprotective effect of inflammation: Implications for the therapy of multiple sclerosis. J. Neuroimmunol., 107 (2), 161-166.
• Holsinger RM., Schnarr J., Henry P., Castelo VT., Fahnestock M., 2000. Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcriptionpolymerase chain reaction: decreased levels in Alzheimer's disease. Brain Res. Mol. Brain Res., 76 (2), 347-354.
• Honea RA., Cruchaga C., Perea RD., Saykin AJ., Burns JM., Weinberger DR., Goate AM., 2013. Characterizing the Role of Brain Derived Neurotrophic Factor Genetic Variation in Alzheimer’s Disease Neurodegeneration. PLoS One, Sep 26;8(9):e76001. doi: 10.1371/journal.pone.0076001
• Horch HW., Katz LC., 2002. BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat. Neurosci., 5, 1177-1184.
• Howells DW., Porritt M., Wong JY., Batchelor PE., Kalnins R., Hughes AJ., Donan GA., 2000. Reduced BDNF mRNA expression in the Parkinson’s diseases substantia nigra. Exp. Neurol., 166 (1), 127-135.
• Huntley GW., Benson DL., Jones EG., Isackson PJ., 1992. Developmental expression of brain derived neurotrophic factor mRNA by neurons of fetal and adult monkey prefrontal cortex. Brain Res. Dev. Brain Res., 70 (1), 53-63.
• Jeon SJ., Rhee SY., Seo JE., Bak HR., Lee SH., Ryu JH., Cheong JH., Shin CY., Kim GH., Lee YS., Ko KH., 2011. Oroxylin A increases BDNF production by activation of MAPK-CREB pathway in rat primary cortical neuronal culture. Neurosci. Res., 69 (3), 214-222.
• Jones KR., Farinas I., Backus C., Reichardt LF., 1994. Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development. Cell, 76, 989-999.
• Karege F., Perret G., Bondolfi G., Schwald M., Bertschy G., Aubry JM., 2002. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res., 109, 143-148.
• Karege F., Bondolfi G., Gervasoni N., Schwald M., Aubry JM., Bertschy G., 2005. Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol. Psychiatry, 57, 1068-1072.
• Kerschensteiner M., Gallmeier E., Behrens L., Leal VV., Misgeld T., Klinkert WE., Kolbeck R., Hoppe E., Oropeza-Wekerle RL., Bartke I., Stadelmann C., Lassmann H., Wekerle H., Hohfeld R., 1999. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J. Exp. Med., 189 (5), 865-870.
• Kobayashi NR., Fan DP., Giehl KM., Bedard AM., Wiegand SJ., Tetzlaff W., 1997. BDNF and NT-4/5 prevent atrophy of rat rubrospinal neurons after cervical axotomy, stimulate GAP-43 and Ta1-tubulin mRNA expression, and promote axonal regeneration. J. Neurosci., 17, 9583-9595.
• Krabbe KS., Nielsen AR., Krogh-Madsen R., Plomgaard P., Rasmussen P., Erikstrup C., Fischer CP., Lindeguard B., Petersen AM., Taudorf S., Secher NH., Pilegaard H., Bruunsgaard H., Pedersen BK., 2007. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia, 50 (2), 431-438.
• Laske C., Stransky E., Leyhe T., Eschweiler GW., Schott K., Langer H., Gawaz M., 2006. Decreased brain-derived neurotrophic factor (BDNF)- and