title: scAAV9-VEGF prolongs the survival of transgenic ALS mice by promoting activation of M2 microglia and the PI3K/Akt pathway.
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.
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Weisong
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.lastname: Di Wen
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang 050000, Hebei, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Yakun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Zhongyao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Huiqian
authors.initials: H
authors.lastname: Lin
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Can
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Dongxiao
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang 050000, Hebei, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, People's Republic of China; Institute of Cardiocerebrovascular Disease, West Heping Road 215, Shijiazhuang 050000, Hebei, People's Republic of China; Neurological Laboratory of Hebei Province, Shijiazhuang 050000, Hebei, People's Republic of China. Electronic address: hebeichunyanli@aliyun.com.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D000229:Dependovirus; D004195:Disease Models, Animal; D007278:Injections, Spinal; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Adeno-associated virus; Amyotrophic lateral sclerosis; Microglia polarization; Vascular endothelial growth factor