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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Format: | Article |
Language: | English |
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Wiley
2016-01-01
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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. |
format | Article |
id | doaj-art-292bd4fa5e2e43939f05e7e86f430b5f |
institution | Kabale University |
issn | 2090-5904 1687-5443 |
language | English |
publishDate | 2016-01-01 |
publisher | Wiley |
record_format | Article |
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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