Amyloid beta up-regulates brain-derived neurotrophic factor production from astrocytes: rescue from amyloid beta-related neuritic degeneration.
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 beta (Abeta) 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 Abeta to elucidate further the role of astrocytes in Abeta toxicity. By using real-time PCR and ELISA analyses, we found that Abeta rapidly induced astrocytes to produce brain-derived neurotrophic factor (BDNF). Abeta42 was more effective than Abeta40 in increasing astroglial BDNF production. Moreover, BDNF treatment rescued the neuronally differentiated human neuroblastoma cells from neuritic degeneration caused by Abeta toxicity. This is the first study to demonstrate that astrocytes are capable of increasing the production of a particular neurotrophic factor in response to Abeta. Our findings also identify BDNF as a potential therapeutic agent for preventing Abeta-related neuritic degeneration.
Kimura
Nobuyuki
N
Laboratory of Disease Control, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba-shi, Ibaraki, Japan. kimura@nibio.go.jp
Takahashi
Masaki
M
Tashiro
Tomoko
T
Terao
Keiji
K
D000682:Amyloid / Q000008:administration & dosage*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D015153:Blotting, Western / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009447:Neuroblastoma; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016704:Synapsins / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
D000682:Amyloid; D019208:Brain-Derived Neurotrophic Factor; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D016704:Synapsins