Sevoflurane Induces Learning and Memory Impairment in Young Mice Through a Reduction in Neuronal Glucose Transporter 3.

Abstract

Sevoflurane, which is widely used in paediatric anaesthesia, induces neural apoptosis in the developing brain and cognitive impairment in young mammals. Glucose hypometabolism is the key pathophysiological modulator of cognitive dysfunction. However, the effects and mechanism of sevoflurane on cerebral glucose metabolism after its use as an anaesthetic and its complete elimination are still unknown. We therefore investigated the influence of sevoflurane on neuronal glucose transporter isoform 3 (GLUT3) expression, glucose metabolism and apoptosis in vivo and in vitro and on neurocognitive function in young mice 24 h after the third exposure to sevoflurane. Postnatal day 14 (P14) mice and neural cells were exposed to 3% sevoflurane 2 h daily for three days. We found that sevoflurane anaesthesia decreased GLUT3 gene and protein expression in the hippocampus and temporal lobe, consistent with a decrease in glucose metabolism in the hippocampus and temporal lobe observed by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET). Moreover, sevoflurane anaesthesia increased the number of TUNEL-positive cells and the levels of Bax, cleaved caspase 3 and cleaved PARP and reduced Bcl-2 levels in the hippocampus and temporal lobe. Young mice exposed to sevoflurane multiple times also showed learning and memory impairment. In addition, sevoflurane inhibited GLUT3 expression in primary hippocampal neurons and PC12 cells. GLUT3 overexpression in cultured neurons ameliorated the sevoflurane-induced decrease in glucose utilization and increase in the apoptosis rate. These data indicate that GLUT3 deficiency may contribute to sevoflurane-induced learning and memory deficits in young mice.

• Authors: Jinpiao Zhu, Zongze Zhang, Junke Jia, Lirong Wang, Qiuyue Yang, Yanlin Wang, Chang Chen
• Journal: Cellular and molecular neurobiology (Cell Mol Neurobiol) Vol. 40 Issue 6 Pg. 879-895 (Aug 2020) ISSN: 1573-6830 [Electronic] United States
• PMID: 31884568 (Publication Type: Journal Article)

Chemical References

• Glucose Transporter Type 3
• RNA, Messenger
• Slc2a3 protein, mouse
• Sevoflurane
• Glucose

Topics

• Aging (metabolism)
• Animals
• Apoptosis (drug effects)
• Brain (metabolism)
• Cell Membrane (metabolism)
• Cells, Cultured
• Glucose (metabolism)
• Glucose Transporter Type 3 (genetics, metabolism)
• Learning
• Male
• Memory Disorders (metabolism, physiopathology)
• Mice
• Mice, Inbred C57BL
• Neurons (metabolism)
• PC12 Cells
• RNA, Messenger (genetics, metabolism)
• Rats
• Sevoflurane (adverse effects)