Environmental Enrichment Attenuated Sevoflurane-Induced Neurotoxicity through the PPAR-γ Signaling Pathway

Abstract EN

Sevoflurane is the most widely used inhaled anesthetic.

Environmental enrichment (EE) can reverse sevoflurane-induced learning and memory impairment in young mice.

However, the mechanism by which EE elicits this effect is unclear.

The peroxisome proliferator-activated receptor (PPAR) regulatory pathway plays a critical role in the regulation of inflammation in central nervous system diseases.

In this study, we investigated whether EE attenuates sevoflurane-induced learning and memory disability via the PPAR signaling pathway.

Six-day-old mice were treated with 3% sevoflurane for 2 hours daily from postnatal day 6 (P6) to P8.

Then, the mice were treated with EE.

The effects of sevoflurane on learning and memory function, PPAR-γ expression in the brain, and the numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and 5-bromodeoxyuridine-positive cells in the hippocampus were determined.

Sevoflurane induced neuronal apoptosis and neurogenesis inhibition, which may impair learning and memory in young mice.

Furthermore, sevoflurane downregulated PPAR-γ expression.

Both EE and the PPAR-γ agonist, rosiglitazone, attenuated sevoflurane-induced neuronal apoptosis, neurogenesis inhibition, and learning and memory impairment.

Our findings suggest that EE ameliorated sevoflurane-induced neurotoxicity and learning and memory impairment through the PPAR-γ signaling pathway.

PPAR-γ may be a potential therapeutic target for preventing or treating sevoflurane-induced neurotoxicity.