scAAV9-VEGF prolongs the survival of transgenic ALS mice by promoting activation of M2 microglia and the PI3K/Akt pathway - PubMed (original) (raw)

. 2016 Oct 1;1648(Pt A):1-10.

doi: 10.1016/j.brainres.2016.06.043. Epub 2016 Jul 5.

Weisong Duan 2, Wan Wang 1, Di Wen 1, Yaling Liu 3, Yakun Liu 2, Zhongyao Li 2, Haojie Hu 1, Huiqian Lin 1, Can Cui 1, Dongxiao Li 1, Hui Dong 3, Chunyan Li 4

Affiliations

scAAV9-VEGF prolongs the survival of transgenic ALS mice by promoting activation of M2 microglia and the PI3K/Akt pathway

Ying Wang et al. Brain Res. 2016.

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease that leads to paralysis and death three to five years after diagnosis in most patients. The disease is incurable, and the mechanism of motoneuron degeneration remains unknown, although research has demonstrated that activated microglia are involved in motor neuron death. Here, we used a simple method to deliver AAV9 virus by direct intrathecal injection and found that scAAV9-VEGF-165 improved the motor performance and prolonged the life span of SOD1-G93A mice. Furthermore, scAAV9-VEGF-165 activated the PI3K/Akt survival pathway and increased the level of Bcl-2, which contributed to the protection of motor neurons. Additionally, scAAV9-VEGF-165 attenuated the expression of classically activated (M1) microglial markers and enhanced the expression of alternatively activated (M2) microglial markers. Taken together, the results of our study suggest that simple, direct intrathecal injection of scAAV9-VEGF-165 may have a curative effect for ALS.

Keywords: Adeno-associated virus; Amyotrophic lateral sclerosis; Microglia polarization; Vascular endothelial growth factor.

Copyright © 2016 Elsevier B.V. All rights reserved.

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