Vascular endothelial growth factor alleviates mitochondrial dysfunction and suppression of mitochondrial biogenesis in models of Alzheimer's disease.

Abstract

PURPOSE:

Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD). As vascular endothelial growth factor (VEGF) has been shown to be protective in AD, the aim of this study was to investigate the effects of VEGF on mitochondrial function in models of AD.

MATERIALS AND METHODS:

Adeno associated virus (AAV)-VEGF was injected into the hippocampus of APP/PS1 mice. Cognitive function was assessed in these mice with use of the Morris water maze (MWM) and β-amyloid (Aβ) levels in the hippocampus were also measured. Cell viability and reactive oxygen species (ROS) levels were determined in the SH-SY5Y cells treated with Aβ25-35 which served as a cell model of AD. Transmission electron microscopy (TEM) was used to evaluate structural changes in mitochondria and mitochondrial DNA (mtDNA) copy number and mitochondrial membrane potential (MMP) were also recorded. Finally, we investigated the effects of VEGF upon mitochondrial biogenesis, autophagy and mitochondrial autophagy (mitophagy) as determined both in vivo and in vitro with western blots.

RESULTS:

VEGF treated mice showed improvements in spatial learning and memory along with reduced Aβ levels. VEGF protected SH-SY5Y cells against Aβ25-35 induced neurotoxicity as demonstrated by increased cell viability and decreased ROS production. Associated with these effects were improvements in mitochondrial structure and function, and increased numbers of mitochondria resulting from stimulation of mitochondrial biogenesis.

CONCLUSIONS:

VEGF alleviates Aβ related patholoy in models of AD. In part, these beneficial effects of VEGF result from protection of mitochondria and stimulation of mitochondrial biogenesis.

• Authors: Xiangtian Liu, Bingcong Chu, Suqin Jin, Maoyu Li, Yingying Xu, Hui Yang, Zhe Feng, Jianzhong Bi, Ping Wang
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 131 Issue 2 Pg. 154-162 (Feb 2021) ISSN: 1563-5279 [Electronic] England
• PMID: 32083964 (Publication Type: Journal Article)

Chemical References

• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse

Topics

• Alzheimer Disease (metabolism)
• Animals
• Cell Line, Tumor
• Cells, Cultured
• Disease Models, Animal
• Hippocampus (drug effects, metabolism)
• Humans
• Male
• Mice
• Mice, Transgenic
• Mitochondria (metabolism)
• Organelle Biogenesis
• Vascular Endothelial Growth Factor A (administration & dosage, metabolism)