No association of Brain-derived neurotrophic factor with striatal dopamine transporter availability in healthy subjects

 

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Abstract

Objective Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in brain plasticity, synaptic function, neuronal survival, learning, and memory formation. We aimed to investigate the association of BDNF with dopamine transporter (DAT) availabilities measured by positron emission tomography (PET) in healthy subjects.

Methods Thirty-five healthy, male subjects without brain injury, neuropsychological disorders were included in this study. The emission data were acquired over 90 mins with 50 frames after injection of 18F-FP-CIT using PET. Binding potentials (BP_NDs) of ventral striatum (VST), caudate nucleus, putamen were measured with the simplified reference tissue method. The serum BDNF level (pg/mL) was measured through enzyme-linked immunosorbent assay method.

Results Thirty-five healthy males with a mean age of 24.4 ± 2.7 years were included in this study. Multiple regression was done to investigate the association between striatal BPNDs from VST, caudate nucleus, putamen and serum BDNF after adjusting for age. None of striatal BPNDs from VST (p=0.8450), caudate nucleus (p=0.4783), and putamen (p=0.7994) were associated with serum BDNF.

Conclusion Striatal DAT availabilities measured from PET were not associated with the serum BDNF in healthy subjects.

Zusammenfassung

Ziel Der Wachstumsfaktor BDNF (Brain-derived neurotrophic factor) ist ein Neurotrophin, das eine Schlüsselrolle bei der Plastizität des Gehirns, der synaptischen Funktion, dem neuronalen Überleben, dem Lernen und der Gedächtnisbildung spielt. Unser Ziel war es, mittels Positronen-Emissions-Tomografie (PET) die Assoziation von BDNF und dem Vorhandensein von Dopamin-Transportern (DAT) bei gesunden Probanden zu untersuchen.

Methoden 35 gesunde, männliche Probanden ohne Hirnverletzungen und neuropsychologische Störungen wurden in diese Studie aufgenommen. Die Emissionsdaten wurden über 90min mit 50 Frames nach Injektion von 18F-FP-CIT mittels PET erfasst. Die Bindungspotenziale (BPNDs) von ventralem Striatum (VST), Nucleus caudatus und Putamen wurden mit der vereinfachten Referenzgewebemethode gemessen. Der Serum-BDNF-Spiegel (pg/mL) wurde mittels ELISA (Enzyme-linked-Immunosorbent-Assay) bestimmt.

Ergebnisse 35 gesunde Männer mit einem Durchschnittsalter von 24,4±2,7 Jahren wurden in diese Studie aufgenommen. Mittels multipler Regression wurde die Assoziation zwischen striatalen BPNDs aus VST, Nucleus caudatus, Putamen und Serum-BDNF nach Altersbereinigung untersucht. Keine der striatalen BPNDs von VST (p=0,8450), Nucleus caudatus (p=0,4783) und Putamen (p=0,7994) waren mit Serum-BDNF assoziiert.

Schlussfolgerung Das mittels PET gemessene Vorhandensein von striatalen DAT war bei gesunden Probanden nicht mit Serum-BDNF assoziiert.

Publication History

Received: 18 February 2021

Accepted after revision: 31 May 2021

Article published online:
13 July 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Edelmann E, Lessmann V, Brigadski T. Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity. Neuropharmacology 2014; 76(C): 610-627 DOI: 10.1016/j.neuropharm.2013.05.043. (PMID: 23791959)
  CrossrefPubMedGoogle Scholar
• 2 Panja D, Bramham CR. BDNF mechanisms in late LTP formation: A synthesis and breakdown. Neuropharmacology 2014; 76(C): 664-676 DOI: 10.1016/j.neuropharm.2013.06.024. (PMID: 23831365)
  CrossrefPubMedGoogle Scholar
• 3 Hernandez-Vara J, Saez-Francas N, Lorenzo-Bosquet C. et al. BDNF levels and nigrostriatal degeneration in "drug naive" Parkinson's disease patients. An "in vivo" study using I-123-FP-CIT SPECT. Parkinsonism Relat Disord 2020; 78: 31-35 DOI: 10.1016/j.parkreldis.2020.06.037. (PMID: 32682292)
  CrossrefPubMedGoogle Scholar
• 4 Hwang KS, Lazaris AS, Eastman JA. et al. Plasma BDNF levels associate with Pittsburgh compound B binding in the brain. Alzheimers Dement (Amst) 2015; 1: 187-193 DOI: 10.1016/j.dadm.2015.01.005. (PMID: 26207261)
  CrossrefPubMedGoogle Scholar
• 5 Lima Giacobbo B, Doorduin J, Klein HC. et al. Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation. Mol Neurobiol 2019; 56: 3295-3312 DOI: 10.1007/s12035-018-1283-6. (PMID: 30117106)
  CrossrefPubMedGoogle Scholar
• 6 Salehi Z, Mashayekhi F. Brain-derived neurotrophic factor concentrations in the cerebrospinal fluid of patients with Parkinson's disease. J Clin Neurosci 2009; 16: 90-93 DOI: 10.1016/j.jocn.2008.03.010. (PMID: 19017558)
  CrossrefPubMedGoogle Scholar
• 7 Ventriglia M, Zanardini R, Bonomini C. et al. Serum brain-derived neurotrophic factor levels in different neurological diseases. Biomed Res Int 2013; 2013: 901082 DOI: 10.1155/2013/901082. (PMID: 24024214)
  CrossrefPubMedGoogle Scholar
• 8 Vaughan RA, Foster JD. Mechanisms of dopamine transporter regulation in normal and disease states. Trends Pharmacol Sci 2013; 34: 489-496 DOI: 10.1016/j.tips.2013.07.005. (PMID: 23968642)
  CrossrefPubMedGoogle Scholar
• 9 Park E. A new era of clinical dopamine transporter imaging using 123I-FP-CIT. J Nucl Med Technol 2012; 40: 222-228 DOI: 10.2967/jnmt.112.111617.
  CrossrefPubMedGoogle Scholar
• 10 Ziebell M, Khalid U, Klein AB. et al. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration. Neurobiol Aging 2012; 33: 428.e421-425 DOI: 10.1016/j.neurobiolaging.2010.11.010. (PMID: 21176997)
  CrossrefPubMedGoogle Scholar
• 11 Frim DM, Uhler TA, Galpern WR. et al. Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci U S A 1994; 91: 5104-5108 DOI: 10.1073/pnas.91.11.5104. (PMID: 8197193)
  CrossrefPubMedGoogle Scholar
• 12 Pak K, Seo S, Kim K. et al. Striatal dopamine transporter changes after glucose loading in humans.. Diabetes Obes Metab 2020; 22: 116-122 DOI: 10.1111/dom.13872. (PMID: 31478329)
  CrossrefPubMedGoogle Scholar
• 13 Piccinni A, Marazziti D, Del Debbio A. et al. Diurnal variation of plasma brain-derived neurotrophic factor (BDNF) in humans: an analysis of sex differences. Chronobiol Int 2008; 25: 819-826 DOI: 10.1080/07420520802387773. (PMID: 18780207)
  CrossrefPubMedGoogle Scholar
• 14 Ferris MJ, Espana RA, Locke JL. et al. Dopamine transporters govern diurnal variation in extracellular dopamine tone. Proc Natl Acad Sci U S A 2014; 111: E2751-2759 DOI: 10.1073/pnas.1407935111. (PMID: 24979798)
  CrossrefPubMedGoogle Scholar
• 15 Lammertsma AA, Hume SP. Simplified reference tissue model for PET receptor studies. Neuroimage 1996; 4: 153-158 DOI: 10.1006/nimg.1996.0066. (PMID: 9345505)
  CrossrefPubMedGoogle Scholar
• 16 Zipursky RB, Meyer JH, Verhoeff NP. PET and SPECT imaging in psychiatric disorders. Can J Psychiatry 2007; 52: 146-157 DOI: 10.1177/070674370705200303. (PMID: 17479522)
  CrossrefPubMedGoogle Scholar
• 17 Hinderberger P, Rullmann M, Drabe M. et al. The effect of serum BDNF levels on central serotonin transporter availability in obese versus non-obese adults: A [(11)C]DASB positron emission tomography study. Neuropharmacology 2016; 110: 530-536 DOI: 10.1016/j.neuropharm.2016.04.030. (PMID: 27108933)
  CrossrefPubMedGoogle Scholar