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The article focuses on a study which evaluates the effects of nitrous oxide and isoflurane on apoptosis and beta-amyloid levels in human neuroglioma cells and primary neurons from mice. In this study, cells or neurons and conditioned media that are exposed to nitrous oxide and isoflurane are harvested at the end of the treatment. Researchers determine the caspase-3 activation, apoptosis, processing of amyloid precursor protein (APP) and beta-amyloid levels. They conclude that apoptosis can enhance aspartyl protease beta-site APP-cleaving enzyme (BACE) levels to help APP processing.

Background: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane, a commonly used anesthetic in children, has been reported to decrease levels of postsynaptic density 95 protein. However, the upstream mechanisms and downstream consequences of the sevoflurane-induced reduction in postsynaptic density 95 protein levels remains largely unknown. We therefore set out to assess whether sevoflurane acts on ubiquitination-proteasome pathway to facilitate postsynaptic density 95 protein degradation.Methods: Six-day-old wild-type mice received anesthesia with 3% sevoflurane 2 h daily for 3 days starting on postnatal day 6. We determined the effects of the sevoflurane anesthesia on mRNA, protein and ubiquitinated levels of postsynaptic density 95 protein in neurons, and synaptosomes and hippocampus of young mice. Cognitive function in the mice was determined at postnatal day 31 by using a Morris water maze. Proteasome inhibitor MG132 and E3 ligase mouse double mutant 2 homolog inhibitor Nutlin-3 were used for the interaction studies.Results: The sevoflurane anesthesia decreased protein, but not mRNA, levels of postsynaptic density 95, and reduced ubiquitinated postsynaptic density 95 protein levels in neurons, synaptosomes, and hippocampus of young mice. Both MG132 and Nutlin-3 blocked these sevoflurane-induced effects. Sevoflurane promoted the interaction of mouse double mutant 2 homolog and postsynaptic density 95 protein in neurons. Finally, MG132 and Nutlin-3 ameliorated the sevoflurane-induced cognitive impairment in the mice.Conclusions: These data suggest that sevoflurane acts on the ubiquitination-proteasome pathway to facilitate postsynaptic density 95 protein degradation, which then decreases postsynaptic density 95 protein levels, leading to cognitive impairment in young mice. These studies would further promote the mechanistic investigation of anesthesia neurotoxicity in the developing brain. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examined the effects of sevoflurane, an inhalation anesthetic, on caspase activation, apoptosis, β-amyloid protein levels and neuroinflammation in the brain tissues of neonatal naïve and Alzheimer disease (AD) transgenic mice. Brain cortex was harvested from the mouse decapitated after sevoflurane anesthesia was administered. The study demonstrated that sevoflurane anesthesia induced caspase activation and apoptosis and even altered amyloid precursor protein processing and increased &beta-;-amyloid protein levels in the brain tissues of neonatal mice. This indicates that neurotoxicity in neonatal mice may be induced by the said anesthetic.