Genome-Wide Screen of the Hippocampus in Aged Rats Identifies Mitochondria, Metabolism and Aging Processes Implicated in Sevoflurane Anesthesia

Abstract

Previous studies have shown multiple mechanisms and pathophysiological changes after anesthesia, and genome-wide studies have been implemented in the studies of brain aging and neurodegenerative diseases.However, the genome-wide gene expression patterns and modulation networks after general anesthesia remains to be elucidated. Therefore, whole transcriptome microarray analysis was used to explore the coding gene expression patterns in the hippocampus of aged rats after sevoflurane anesthesia. Six hundred and thirty one upregulated and 183 downregulated genes were screened out, then 44 enriched terms of biological process, 16 of molecular function and 18 of the cellular components were identified by Gene Ontology (GO) and KEGG analysis. Among them, oxidative stress, metabolism, aging, and neurodegeneration were the most enriched biological processes and changed functions. Thus, involved genes of these processes were selected for qPCR verification and a good consistency was confirmed. The potential signaling pathways were further constructed including mitochondrion and oxidative stress-related Hifs-Prkcd-Akt-Nfe2l2-Sod1 signaling, multiple metabolism signaling (Scd2, Scap-Hmgcs2, Aldh18a1-Glul and Igf1r), as well as aging and neurodegeneration related signaling (Spidr-Ercc4-Cdkn1a-Pmaip1 and Map1lc3b). These results provide potential therapeutic gene targets for brain function modulation and memory formation process after inhaled anesthesia in the elderly, which could be valuable for preventing postoperative brain disorders and diseases, such as perioperative neurocognitive disorders (PND), from the genetic level in the future.

TRPV1 Antagonist Prevents Neonatal Sevoflurane-Induced Synaptic Abnormality and Cognitive Impairment in Mice Through Regulating the Src/Cofilin Signaling Pathway

“…Because the contextual fear conditioning was the hippocampal dependent learning, and tone fear conditioning was hippocampal independent learning ( Phillips and LeDoux, 1992 ; Medina et al, 2002 ). It is possible that the amygdala function was unlikely impaired and the expression of TRPV1 in the amygdala remained unchanged, thus sevoflurane did not induce memory impairment which was consistent with the previous studies ( Ni et al, 2020 ; Wang et al, 2020 ).…”

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet

“…While some authors showed a lack of expression of HMGCS2 in astrocytes and neurons ( Thevenet et al, 2016 ), the latest studies confirm the astrocytic expression of HMGCS mRNA ( Song et al, 2021 ). HMGCS has been found to be abundantly expressed in the astrocytes of the optic nerve ( Metwally et al, 2019 ) and other glial cells ( Wang et al, 2016 ) and various brain areas ( Shao et al, 2019 ; Kondo et al, 2020 ), including the hippocampus ( Wang et al, 2020 ). Moreover, HMGCS2 has been defined as an autophagy regulator ( Hu et al, 2017 ), which raises the role of ketone metabolism as an autophagy enhancer.…”

[Retracted] Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane‐Induced Cell Toxicity

“…Therefore, it is no doubt that mitochondrial abnormality inevitably leads to neural dysfunction. It has been demonstrated that mitochondria are the targets of sevoflurane-induced neural toxicity [ 8 , 9 ]. Sevoflurane exposure induces neural toxicity by initiating mitochondrial apoptotic pathway, disturbing the balance of mitochondrial dynamics and mitophagy.…”