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Neural Plast. 2016;2016:4145708. doi: 10.1155/2016/4145708. Epub 2016 Jan 10.

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

Author information

1
Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, Germany.
2
Institute of Clinical Chemistry and Pathobiochemistry, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
3
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany.
4
German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany.
5
Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120 Magdeburg, Germany; Center of Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany.

Abstract

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.

PMID:
26881108
PMCID:
PMC4736975
DOI:
10.1155/2016/4145708
[Indexed for MEDLINE]
Free PMC Article

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