Sevoflurane Exposure in Neonates Perturbs the Expression Patterns of Specific Genes That May Underly the Observed Learning and Memory Deficits

Abstract

Exposure to commonly used anesthetics leads to neurotoxic effects in animal models—ranging from cell death to learning and memory deficits. These neurotoxic effects invoke a variety of molecular pathways, exerting either immediate or long-term effects at the cellular and behavioural levels. However, little is known about the gene expression changes following early neonatal exposure to these anesthetic agents. We report here on the effects of sevoflurane, a commonly used inhalational anesthetic, on learning and memory and identify a key set of genes that may likely be involved in the observed behavioural deficits. Specifically, we demonstrate that sevoflurane exposure in postnatal day 7 (P7) rat pups results in subtle, but distinct, memory deficits in the adult animals that have not been reported previously. Interestingly, when given intraperitoneally, pre-treatment with dexmedetomidine (DEX) could only prevent sevoflurane-induced anxiety in open field testing. To identify genes that may have been altered in the neonatal rats after sevoflurane and DEX exposure, specifically those impacting cellular viability, learning, and memory, we conducted an extensive Nanostring study examining over 770 genes. We found differential changes in the gene expression levels after exposure to both agents. A number of the perturbed genes found in this study have previously been implicated in synaptic transmission, plasticity, neurogenesis, apoptosis, myelination, and learning and memory. Our data thus demonstrate that subtle, albeit long-term, changes observed in an adult animal’s learning and memory after neonatal anesthetic exposure may likely involve perturbation of specific gene expression patterns.