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29-04-2023 | Metformin | Original Article

Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway

Authors: Pei Fan, Yuying Lu, Haidong Wei, Kui Wang, Pengyu Jia, Yuanyuan Zhang, Yan Zhang, Tianyue Wang, Liufei Yang, Jing Zhao, Shuyue Zhang, Haixia Lu, Xinlin Chen, Yong Liu, Pengbo Zhang

Published in: Metabolic Brain Disease | Issue 6/2023

Abstract

Anesthetics such as sevoflurane are commonly administered to infants and children. However, the possible neurotoxicity caused by prolonged or repetitive exposure to it should be a concern. The neuroprotective effects of metformin are observed in many models of neurological disorders. In this study, we investigated whether metformin could reduce the developmental neurotoxicity induced by sevoflurane exposure in neonatal rats and the potential mechanism. Postnatal day 7 (PND 7) Sprague-Dawley rats and neural stem cells (NSCs) were treated with normal saline or metformin before sevoflurane exposure. The Morris water maze (MWM) was used to observe spatial memory and learning at PND 35–42. Immunofluorescence staining was used to detect neurogenesis in the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus at PND 14. MTT assays, immunofluorescence staining, and TUNEL staining were used to assess the viability, proliferation, differentiation, and apoptosis of NSCs. Western blotting and ELISA were used to assess the protein expression of cleaved caspase-3, nuclear factor erythroid 2-related factor 2 (Nrf2), and glucose-6-phosphate dehydrogenase (G6PD) pathway-related molecules. Exposure to sevoflurane resulted in late cognitive defects, impaired neurogenesis in both the SVZ and SGZ, reduced NSC viability and proliferation, increased NSC apoptosis, and decreased protein expression of G6PD in vitro. Metformin pretreatment attenuated sevoflurane-induced cognitive functional decline and neurogenesis inhibition. Metformin pretreatment also increased the protein expression of Nrf2 and G6PD. However, treatment with the Nrf2 inhibitor, ML385 or the G6PD inhibitor, dehydroepiandrosterone (DHEA) reversed the protective effect of metformin on sevoflurane-induced NSC damage in vitro. Our findings suggested that metformin could reduce sevoflurane-induced neurogenesis damage and neurocognitive defects in the developing rat brain by influencing the Nrf2/G6PD signaling pathways.

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Title: Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway
Authors: Pei Fan
Yuying Lu
Haidong Wei
Kui Wang
Pengyu Jia
Yuanyuan Zhang
Yan Zhang
Tianyue Wang
Liufei Yang
Jing Zhao
Shuyue Zhang
Haixia Lu
Xinlin Chen
Yong Liu
Pengbo Zhang
Publication date: 29-04-2023
Publisher: Springer US
Keywords: Metformin
Sevoflurane
Published in: Metabolic Brain Disease / Issue 6/2023
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-023-01218-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Metformin attenuates sevoflurane-induced neurogenesis damage and cognitive impairment: involvement of the Nrf2/G6PD pathway

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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