The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice.

Abstract

Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer's disease (AD) rats through inhibition of Aβ production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3× Tg) AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1α (PDHE1α), and the post synaptic density protein 95 (PSD95), was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Aβ and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1) and an increase in fusion protein Mitofusin 2 (Mfn2). These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction-related neuronal degenerative diseases.

• Authors: Yijing Chen, Shuangxue Han, Xiuxian Huang, Jiazuan Ni, Xiaoyang He
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 17 Issue 2 (Jan 27 2016) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 26828481 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Flavonoids
• tau Proteins
• icariin

Topics

• Alzheimer Disease (drug therapy, metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Biological Transport (drug effects)
• Cells, Cultured
• Chick Embryo
• Disease Models, Animal
• Flavonoids (administration & dosage, pharmacology)
• Hippocampus (cytology)
• Mice
• Mitochondria (drug effects, metabolism)
• Mitochondrial Dynamics (drug effects)
• Mitochondrial Size (drug effects)
• Neurons (drug effects, metabolism)
• tau Proteins (metabolism)