Azaltılmış Beyin Kaynaklı Nörotrofik Faktörün (BDNF), Fare Karaciğer ve Böbrek Dokusuna Apoptotik Etkileri

Amaç: Beyin kökenli nörotrofik faktör (BDNF), merkezi ve periferik sinir sisteminde belirli nöron grupları üzerine etki ederek, nöron ve sinapsların gelişimini ve farklılaşmasını, bunun yanında nöronal sağkalımı desteklemektedir. Periferik dokularda ise BDNF'nin apoptoz ile direkt ilişkisi bilinmemektedir. Bu çalışmada, karaciğer ve böbrek dokularında BDNF'nin apoptoz ile ilişkisi ve bu dokulardaki BDNF reseptörlerinin yoğunluk ve dağılımının histolojik ve immünohistokimyasal yöntemler kullanılarak araştırılması amaçlanmıştır. Yöntemler: Araştırmada 7 adet yabanıl tip ve 7 adet BDNF heterozigot (BDNF düzeyleri yarı yarıya azaltılmış) erkek fare kullanılmıştır. Karaciğer ve böbrek dokusunda apoptozun varlığını araştırmak amacıyla Kaspaz-3 ve TUNEL immünohistokimyasal boyamaları gerçekleştirilmiş ve apoptoza giren hücreler sayılarak gruplar arası karşılaştırma yapılmıştır. BDNF reseptörleri olan tropomiyozin-ilişkili kinaz B (TrkB) ve nerve growth factor receptor p75 (NGFR p75)'in karaciğer ve böbrek dokularındaki yoğunluk ve dağılımı da immünohistokimyasal analizler ile incelenmiştir. Bulgular: Kaspaz-3 ve TUNEL immünohistokimyasal boyamaları sonucunda kontrol grubuna göre, BDNF heterozigot gruba ait kesitlerde daha fazla sayıda apoptoza girmiş hücre sayılmıştır (p

Apoptotic Effects of Reduced Brain Derived Neurotrophic Factor (BDNF) on Mouse Liver and Kidney

Objective: Brain-derived neurotrophic factor (BDNF) promotes the development and differentiation of neurons and synapses, as well as neuronal survival, by acting on specific neuronal groups in the central and peripheral nervous systems. However, the direct effect of BDNF on apoptosis in peripheral tissues is not known. The aim of this study was to investigate the relationship between BDNF and apoptosis, and the density and distribution of BDNF receptors in liver and kidney tissues by histological and immunehistochemical methods. Results: As a result of Caspase-3 and TUNEL immunehistochemical staining, more cells were counted to enter the apoptotic process in sections of BDNF heterozygous group compared to control group (p<0.0001). In both groups TrkB and NGFR p75 receptors in liver and kidney tissues were determined in trace amounts, but there was no difference in intensity and distribution between the studied groups. Conclusion: According to our histological and immunehistochemical stainings and statistical analysis of cell count between groups, it was found that BDNF is protective against apoptosis in liver and kidney. The lack of difference between the studied groups in terms of intensity and distribution of BDNF receptors, suggests that BDNF receptor distribution in the liver and kidney tissues may be different from the nervous system or that BDNF may differ in affinity for these receptors.

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  • Binder DK, Scharfman HE. Brain-derived neurotrophic factor. Growth Factors. 2004; 22:123-31.
  • Lewin GR, Barde YA. Physiology of neurotrophins. Annu Rev Neurosci. 1996; 19:289-317.
  • Barde YA, Edgar D, Thoenen H. Purification of a new neurotrophic factor from mammalian brain. EMBO Journal. 1982; 1:549-53.
  • Götz R, Köster R, Winkler C, et al. Neurotrophin-6 is a new member of the nerve growth factor family. Nature. 1994; 372:266-9.
  • Hallböök F, Ibanez CF, Persson H. Evolutionary studies of the nerve growth factor family reveal a novel member abundantly expressed in Xenopus ovary. Neuron. 1991; 6:845-58.
  • Hohn A, Leibrock J, Bailey K, et al. Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family. Nature. 1990; 344:339-41.
  • Abidin I, Eysel UT, Lessmann V, et al. Impaired GABAergic inhibition in the visual cortex of brain- derived neurotrophic factor heterozygous knockout mice. J Physiol. 2008; 586:1885-901.
  • Acheson A, Conover JC, Fandl JP, et al. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995; 374:450-3.
  • Huang EJ, Reichardt LF. Neurotrophins: Roles in neuronal development and function. Annu Rev Neurosci. 2001; 24:677-736.
  • Matthews VB, Astrom MB, Chan MH, et al. Brain derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP activated protein kinase. Diabetologia. 2009; 52:1409-18.
  • Krabbe KS, Nielsen AR, Krogh-Madsen R, et al. Brain- derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007; 50:431-8.
  • Hacioglu G, Senturk A, Ince I, et al. Assessment of oxidative neurotrophic factor heterozygous mice in acute stress model. Iran J Basic Med Sci. 2016; 19:388-93.
  • Yamada K, Nabeshima T. Brain-derived neurotrophic factor/TrkB signaling in memory processes. J Pharmacol Sci. 2003; 91:267-70.
  • Cassiman D, Denef C, Desmet VJ, et al. Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors. Hepatology. 2001; 33:148-58.
  • Guo D, Hou X, Zhang H, et al. More expressions of BDNF and TrkB in multiple hepatocellular carcinoma and anti-BDNF or K252a induced apoptosis, supressed invasion of HepG2 and HCCLM3 cells. J Exp Clin Cancer Res. 2011; 30:97-105.
  • Lomen-Hoerth C, Shooter EM. Widespread neurotrophin receptor expression in the immune system and other nonneuronal rat tissues. J Neurochem. 1995; 64:1780-9.
  • Lommatzsch M, Braun A, Mannsfeldt A, et al. Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target derived neurotrophic functions. Am J Pathol. 1999; 155:1183-93.
  • Mousavi K, Jasmin BJ. BDNF is expressed in skeletal muscle satellite cells and inhibits myogenic differentiation. J Neurosci. 2006; 26:5739-49.
  • Serra-Millas M. Are the changes in the peripheral brain-derived neurotrophic factor levels due to platelet activation? World J Psychiatry. 2016; 6:84-101.
  • Vivacqua G, Renzi A, Carpino G, et al. Expression of brain derivated neurotrophic factor and of its receptors: TrKB and p75NT in normal and bile duct ligated rat liver. Ital J Anat Embryol. 2014; 119:111-29.
  • Zhou XF, Rush RA. Localization of neurotrophin-3- like immunoreactivity in peripheral tissues of the rat. Brain Res. 1993; 621:189-99.
  • Barrett GL. The p75 neurotrophin receptor and neuronal apoptosis. Prog Neurobiol. 2000; 61:205-29.
  • Friedman WJ. Neurotrophins induce death of hippocampal neurons via the p75 receptor. J Neurosci. 2000; 20:6340-46.
  • Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011; 10:209-19.
  • Ukropec J, Ukropcova B, Kurdiova T, et al. Adipose tissue and skeletal muscle plasticity modulates metabolic health. Arch Physiol Biochem. 2008; 114:357-68.
  • Cummings MC, Winterfold CM, Walker NI. Apoptosis. Am J Surg Pathol. 1997; 21:88-101.
  • Mak T. The E. Donnall Thomas Lecture-apoptosis: "tis death that makes life live". Biol. Blood Marrow Transplant. 2003; 9:483-8.
  • Elmore S. Apoptosis: A review of programmed cell death. Toxicol. Pathol. 2007; 35:495-516.
  • Güleş Ö, Eren Ü. [Methods for Detection of Apoptosis]. Y.Y.Ü.Veteriner Fakültesi Dergisi. 2008; 2:73-8.
  • Wyllie AH, Kerr JF, Currie AR. Cell death: the significance of apoptosis. Int Rev Cytol. 1980; 68:251- 306.
  • Beck T, Lindholm D, Castren E, et al. Brain-derived neurotrophic factor protects against ischemic cell damage in rat hippocampus. J Cereb Blood Flow Metab. 1994; 14:689-92.
  • Kokaia Z, Nawa H, Uchino H, et al. Regional brain- derived neurotrophic factor mRNA and protein levels following transient forebrain ischemia in the rat. Brain Res Mol Brain Res. 1996; 38:139-44.
  • Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998; 281:1312-16.
  • Almeida RD, Manadas BJ, Melo CV, et al. Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ. 2005; 12:1329-43.
  • Korte M, Carroll P, Wolf E, et al. Hippocampal long- term potentiation is impaired in mice lacking brain- derived neurotrophic factor. Proc Natl Acad Sci USA. 1995; 92:8856-60.
  • Yamamoto M, Sobue G, Yamamoto K, et al. Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75NGFR, TrKA, TrKB, and TrKC) in the adult human peripheral nervous system and nonneural tissues. Neurochem Res. 1996; 21:929-38.
  • Shibayama E, Koizumi H. Cellular localization of the TrK neurotrophin receptor family in human non- neuronal tissues. Am J Pathol. 1996; 148:1807-18.
Dicle Tıp Dergisi-Cover
  • ISSN: 1300-2945
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1963
  • Yayıncı: Cahfer GÜLOĞLU
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