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Amyloid β up‐regulates brain‐derived neurotrophic factor production from astrocytes: Rescue from amyloid β‐related neuritic degeneration
Author(s) -
Kimura Nobuyuki,
Takahashi Masaki,
Tashiro Tomoko,
Terao Keiji
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20984
Subject(s) - neurotrophic factors , astrocyte , brain derived neurotrophic factor , senile plaques , neuroscience , neurotrophin , neurodegeneration , alzheimer's disease , amyloid (mycology) , biology , medicine , pathology , disease , central nervous system , receptor , biochemistry
Astrocytes, the most abundant type of glia in the brain, are considered to play a key role in Alzheimer's disease (AD) pathologies. In a cell culture study, we have previously shown that astroglial responses against amyloid β (Aβ) occur before obvious neuronal damage could be detected, suggesting the possibility that astrocytes might be an attractive therapeutic target for treating AD. In the present study, we investigated astroglial gene expression changes in response to Aβ to elucidate further the role of astrocytes in Aβ toxicity. By using real‐time PCR and ELISA analyses, we found that Aβ rapidly induced astrocytes to produce brain‐derived neurotrophic factor (BDNF). Aβ42 was more effective than Aβ40 in increasing astroglial BDNF production. Moreover, BDNF treatment rescued the neuronally differentiated human neuroblastoma cells from neuritic degeneration caused by Aβ toxicity. This is the first study to demonstrate that astrocytes are capable of increasing the production of a particular neurotrophic factor in response to Aβ. Our findings also identify BDNF as a potential therapeutic agent for preventing Aβ‐related neuritic degeneration. © 2006 Wiley‐Liss, Inc.