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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Dihydroartemisinin Ameliorates Decreased Neuroplasticity-Associated Proteins and Excessive Neuronal Apoptosis in APP/PS1 Mice

Author(s): Yueyang Zhao, Zhimin Long, Yuanjie Liu, Min Luo, Yu Qiu, Nur F.B. Idris, Aijia Song, Kejian Wang* and Guiqiong He*

Volume 17 , Issue 10 , 2020

Page: [916 - 925] Pages: 10

DOI: 10.2174/1567205017666201215124746

Price: $65


Background: Alzheimer's disease (AD) is one of the worst neurodegenerative disorders worldwide, with extracellular senile plaques (SP), subsequent intracellular neurofibrillary tangles (NFTs) and final neuron loss and synaptic dysfunction as the main pathological characteristics. Excessive apoptosis is the main cause of irreversible neuron loss. Thus, therapeutic intervention for these pathological features has been considered a promising strategy to treat or prevent AD. Dihydroartemisin (DHA) is a widely used first-line drug for malaria. Our previous study showed that DHA treatment significantly accelerated Aβ clearance, improved memory and cognitive deficits in vivo and restored autophagic flux both in vivo and in vitro.

Methods: The present study intended to explore the neuroprotective effect of DHA on neuron loss in APP/PS1 double-transgenic mice and the underlying mechanisms involved. Transmission electron microscope (TEM) analysis showed that DHA significantly reduced the swollen endoplasmic reticulum (ER) in APP/PS1 mice. Western blot analysis indicated that DHA upregulated the level of NeuN, NeuroD, MAP2, and synaptophysin and promoted neurite outgrowth. Meanwhile, DHA greatly corrected the abnormal levels of Brain-derived neurotrophic factor (BDNF) and rescued the neuronal loss in the hippocampal CA1 area. Western blot analysis revealed that DHA notably down-regulated the protein expression of full length caspase-3, cleaved caspase-3 and Bax. In parallel, the expression of the anti-apoptotic protein Bcl-2 increased after oral DHA treatment.

Results:Altogether, these results indicate that DHA protected AD mice from neuron loss via promoting the expression of BDNF and other neuroplasticity-associated proteins and suppressing the inhibition of neuronal apoptosis.

Keywords: Alzheimer`s disease, amyloid-beta, dihydroartemisinin, apoptosis, synaptophysin, BDNF.

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