Abstract
Amyotrophic lateral sclerosis (ALS) is an adult-onset, chronic, progressive, and fatal neurodegenerative disease that leads to progressive atrophy and weakness of the muscles throughout the body. Herein, we found that the intrathecal injection of adeno-associated virus (AAV)-delivered VEGF in SOD1-G93A transgenic mice, as well as ALS mice, could significantly delay disease onset and preserve motor functions and neurological functions, thus prolonging the survival of mice models. Moreover, we found that VEGF treatment could induce the elevated expression of aromatase, which is a key enzyme in estrogen synthesis, in neurons but not in astrocytes. On the other hand, the changes in the expression of oxidative stress-related factors HO-1 and GCLM and autophagy-related proteins p62 and LC3II upon the administration of VEGF revealed the involvement of oxidative stress and autophagy underlying the downstream of the VEGF-induced mitigation of ALS. In conclusion, this study proved the protective effects of VEGF in the onset and development of ALS and revealed the involvement of estrogen, oxidative stress and autophagy in the VEGF-induced alleviation of ALS. Our results highlighted the potential of VEGF as a promising therapeutic agent in the treatment of ALS.
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Funding
This work was financially supported by the Natural Science Foundation of Shandong Province Youth Fund (No. ZR2020QH126 and ZR2020QH124), Zibo city key research and development plan (2019ZC010137) and TCM science and technology Project of Shandong Province (2021Q048).
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YW and YLL designed this program. YW, JXZ and YYL performed the experiments. JXZ, SS and CYS conducted the data collection and analysis. SS and YW produced the manuscript, which was checked by CMS, QL, JQL and HJ. All the authors have confirmed the submission of this manuscript.
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Communicated by Sreedharan Sajikumar.
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Wang, Y., Sun, S., Zhai, J. et al. scAAV9-VEGF alleviates symptoms of amyotrophic lateral sclerosis (ALS) mice through regulating aromatase. Exp Brain Res 241, 2817–2827 (2023). https://doi.org/10.1007/s00221-023-06721-7
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DOI: https://doi.org/10.1007/s00221-023-06721-7