Geniposide Alleviates Amyloid-Induced Synaptic Injury by Protecting Axonal Mitochondrial Trafficking

Synaptic and mitochondrial pathologies are early events in the progression of Alzheimer's disease (AD). Normal axonal mitochondrial function and transport play crucial roles in maintaining synaptic function by producing high levels of adenosine triphosphate and buffering calcium. However, there...

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Published inFrontiers in cellular neuroscience Vol. 10; p. 309
Main Authors Zhang, Haijing, Zhao, Chunhui, Lv, Cui, Liu, Xiaoli, Du, Shijing, Li, Zhi, Wang, Yongyan, Zhang, Wensheng
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 25.01.2017
Frontiers Media S.A
Subjects
Adenosine triphosphate
Alzheimer's disease
Animal cognition
ATP
Calcium buffering
Cytochrome
Hippocampus
Homeostasis
Injuries
Laboratory animals
Mitochondria
Morphology
Neurons
Neuroprotection
Neuroscience
Pathogenesis
Peptides
Science
Signal transduction
Synaptic density
Beijing China
St Louis Missouri
United States > US
China
axonal transport
geniposide
mitochondrial trafficking
synaptic loss
amyloid β
spine morphology
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Summary:Synaptic and mitochondrial pathologies are early events in the progression of Alzheimer's disease (AD). Normal axonal mitochondrial function and transport play crucial roles in maintaining synaptic function by producing high levels of adenosine triphosphate and buffering calcium. However, there can be abnormal axonal mitochondrial trafficking, distribution, and fragmentation, which are strongly correlated with amyloid-β (Aβ)-induced synaptic loss and dysfunction. The present study examined the neuroprotective effect of geniposide, a compound extracted from gardenia fruit in Aβ-treated neurons and an AD mouse model. Geniposide alleviated Aβ-induced axonal mitochondrial abnormalities by increasing axonal mitochondrial density and length and improving mitochondrial motility and trafficking in cultured hippocampal neurons, consequently ameliorating synaptic damage by reversing synaptic loss, addressing spine density and morphology abnormalities, and ameliorating the decreases in synapse-related proteins in neurons and APPswe/PS1dE9 mice. These findings provide new insights into the effects of geniposide administration on neuronal and synaptic functions under conditions of Aβ enrichment.
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Edited by: Hansen Wang, University of Toronto, Canada
These authors have contributed equally to this work.
Reviewed by: Stefano L. Sensi, University of California, Irvine, USA; P. Hemachandra Reddy, Texas Tech University Health Sciences Center, USA; Oliver Wirths, University of Göttingen, Germany
ISSN:1662-5102
1662-5102
DOI:10.3389/fncel.2016.00309