Just like how a sculptor can mold clay into different shapes, the developing brain is highly moldable and can be influenced by various factors. One crucial factor is the use of anesthetics during medical procedures for children. Researchers have investigated the effects of low-dose Propofol, an anesthetic commonly used in pediatric medicine, on the development of the brain. Through behavioral tests conducted on mice, it was discovered that low-dose Propofol exposure actually enhanced spatial cognitive abilities. This increase in cognitive function was accompanied by an increase in neurogenesis, the formation of new neurons, in the hippocampus and cultured neural stem cells (NSCs). Further analysis revealed that low-dose Propofol activated oxidative phosphorylation (OXPHOS), a process that generates energy in cells, particularly in NSCs. Key to this activation was the upregulation of PGC-1α, a master regulator of mitochondrial metabolism. Inhibition of PGC-1α reversed the effects of low-dose Propofol on neurogenesis and OXPHOS. These findings shed light on a previously unknown mechanism through which low-dose Propofol impacts brain development. Understanding these processes can help ensure the safe and optimal use of low-dose Propofol in pediatric anesthesia. To delve deeper into this intriguing research, explore the full article!

BackgroundDeveloping brain is highly plastic and can be easily affected. Growing pediatric usage of anesthetics during painless procedures has raised concerns about the effect of low-dose anesthetics on neurodevelopment. It is urgent to ascertain the neuronal effect of low-dose Propofol, a widely used anesthetic in pediatrics, on developing brains.MethodsThe behavioral tests after neonatal exposure to low-dose/high-dose Propofol in mice were conducted to clarify the cognitive effect. The nascent cells undergoing proliferation and differentiation stage in the hippocampus and cultured neural stem cells (NSCs) were further identified. In addition, single-nuclei RNA sequencing (snRNA-seq), NSCs bulk RNA-seq, and metabolism trials were performed for pathway investigation. Furthermore, small interfering RNA and stereotactic adenovirus injection were, respectively, used in NSCs and hippocampal to confirm the underlying mechanism.ResultsBehavioral tests in mice showed enhanced spatial cognitive ability after being exposed to low-dose Propofol. Activated neurogenesis was observed both in hippocampal and cultured NSCs. Moreover, transcriptome analysis of snRNA-seq, bulk RNA-seq, and metabolism trials revealed a significantly enhanced oxidative phosphorylation (OXPHOS) level in NSCs. Furthermore, PGC-1α, a master regulator in mitochondria metabolism, was found upregulated after Propofol exposure both in vivo and in vitro. Importantly, downregulation of PGC-1α remarkably prevented the effects of low-dose Propofol in activating OXPHOS and neurogenesis.ConclusionsTaken together, this study demonstrates a novel alteration of mitochondrial function in hippocampal neurogenesis after low-dose Propofol exposure, suggesting the safety, even potentially beneficial effect, of low-dose Propofol in pediatric use.

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