Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons

The neurotrophin brain derived neurotrophic factor (BDNF) is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism...

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Main Authors: Bianca Seifert, Robert Eckenstaler, Raik Rönicke, Julia Leschik, Beat Lutz, Klaus Reymann, Volkmar Lessmann, Tanja Brigadski
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2016/4145708
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author Bianca Seifert
Robert Eckenstaler
Raik Rönicke
Julia Leschik
Beat Lutz
Klaus Reymann
Volkmar Lessmann
Tanja Brigadski
author_facet Bianca Seifert
Robert Eckenstaler
Raik Rönicke
Julia Leschik
Beat Lutz
Klaus Reymann
Volkmar Lessmann
Tanja Brigadski
author_sort Bianca Seifert
collection DOAJ
description The neurotrophin brain derived neurotrophic factor (BDNF) is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism underlying, for example, Alzheimer’s disease (AD). To analyze the role of BDNF transport in AD, live cell imaging of fluorescently labeled BDNF was performed in hippocampal neurons of different AD model systems. BDNF and APP colocalized with low incidence in vesicular structures. Anterograde as well as retrograde transport of BDNF vesicles was reduced and these effects were mediated by factors released from hippocampal neurons into the extracellular medium. Transport of BDNF was altered at a very early time point after onset of human APP expression or after acute amyloid-beta(1-42) treatment, while the activity-dependent release of BDNF remained unaffected. Taken together, extracellular cleavage products of APP induced rapid changes in anterograde and retrograde transport of BDNF-containing vesicles while release of BDNF was unaffected by transgenic expression of mutated APP. These early transport deficits might lead to permanently impaired brain functions in the adult brain.
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institution Kabale University
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series Neural Plasticity
spelling doaj-art-292bd4fa5e2e43939f05e7e86f430b5f2025-02-03T05:53:31ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/41457084145708Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal NeuronsBianca Seifert0Robert Eckenstaler1Raik Rönicke2Julia Leschik3Beat Lutz4Klaus Reymann5Volkmar Lessmann6Tanja Brigadski7Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, GermanyInstitute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, GermanyInstitute of Clinical Chemistry and Pathobiochemistry, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, GermanyInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, GermanyInstitute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, GermanyGerman Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, GermanyInstitute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, GermanyInstitute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, GermanyThe neurotrophin brain derived neurotrophic factor (BDNF) is an important growth factor in the CNS. Deficits in transport of this secretory protein could underlie neurodegenerative diseases. Investigation of disease-related changes in BDNF transport might provide insights into the cellular mechanism underlying, for example, Alzheimer’s disease (AD). To analyze the role of BDNF transport in AD, live cell imaging of fluorescently labeled BDNF was performed in hippocampal neurons of different AD model systems. BDNF and APP colocalized with low incidence in vesicular structures. Anterograde as well as retrograde transport of BDNF vesicles was reduced and these effects were mediated by factors released from hippocampal neurons into the extracellular medium. Transport of BDNF was altered at a very early time point after onset of human APP expression or after acute amyloid-beta(1-42) treatment, while the activity-dependent release of BDNF remained unaffected. Taken together, extracellular cleavage products of APP induced rapid changes in anterograde and retrograde transport of BDNF-containing vesicles while release of BDNF was unaffected by transgenic expression of mutated APP. These early transport deficits might lead to permanently impaired brain functions in the adult brain.http://dx.doi.org/10.1155/2016/4145708
spellingShingle Bianca Seifert
Robert Eckenstaler
Raik Rönicke
Julia Leschik
Beat Lutz
Klaus Reymann
Volkmar Lessmann
Tanja Brigadski
Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
Neural Plasticity
title Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
title_full Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
title_fullStr Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
title_full_unstemmed Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
title_short Amyloid-Beta Induced Changes in Vesicular Transport of BDNF in Hippocampal Neurons
title_sort amyloid beta induced changes in vesicular transport of bdnf in hippocampal neurons
url http://dx.doi.org/10.1155/2016/4145708
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