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Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen–glucose deprivation and reoxygenation

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Abstract

Astrocyte-specific glutamate transporter subtype 1 (GLT-1) plays an important role in influencing glutamate excitatory toxicity and preventing the death of excitatory toxic neurons. Although the mammalian target of rapamycin (mTOR)/protein kinase B(Akt)/nuclear factor kappa B signaling cascade is involved in the upregulation of astrocytic GLT-1 in oxygen–glucose deprivation (OGD), it is unclear whether the mTOR/Akt pathway is involved in astrocytic GLT-1 upregulation in OGD and reoxygenation (OGD/R). In this study, we found that the treatment of cultured astrocytes with rapamycin and triciribine led to the decreased astrocytes’ protrusions, smaller nuclei, and an increased apoptotic rate. The inhibitors of mTOR complex 1 significantly increased the expression levels of phosphorylated Akt-Ser473 (p-Akt), phosphorylated Akt-Thr308(p-Akt), and GLT-1, while Akt-specific inhibitors blocked GLT-1 expression, suggesting that the mTOR/Akt pathway is involved in GLT-1 upregulation. We further demonstrated that astrocytes under OGD/R adapted to environmental changes through the mTOR/Akt pathway, mainly by altering cell morphology and apoptosis and upregulating the expression levels of p-Akt and GLT-1. Our results suggested that astrocytes may adapt to short-term ischemic–reperfusion injury by regulating cell morphology, apoptosis and GLT-1 upregulation.

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Acknowledgements

We are grateful for the helpful comments from members of the Organization Stem Cell Research Institute. This work was supported by grants from the National Natural Science Foundation of China (No. 81870966 to J.YF.). All of the authors declare that they do not have any conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Second Clinical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China

    Mi Li, Jingmei Yu, Huan Deng, Shansha Xie, Qiuling Li, Yuping Zhao, Shubin Yin & Yi-Fei Ji

  2. Department of Neurology, Yilong County People’s Hospital, Nanchong, Sichuan, People’s Republic of China

    Mi Li

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  1. Mi Li
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  2. Jingmei Yu
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  3. Huan Deng
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Correspondence to Yi-Fei Ji.

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Communicated by Sreedharan Sajikumar.

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Li, M., Yu, J., Deng, H. et al. Upregulation of glutamate transporter 1 by mTOR/Akt pathway in astrocyte culture during oxygen–glucose deprivation and reoxygenation. Exp Brain Res 241, 201–209 (2023). https://doi.org/10.1007/s00221-022-06514-4

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