title: Environmental Enrichment Attenuated Sevoflurane-Induced Neurotoxicity through the PPAR-γ Signaling Pathway.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Shanghai East Hospital, Tongji University School of Medicine, No. 150, Jimo Road, Shanghai 200120, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai Medical College of Fudan University, Shanghai 200031, China.
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai Medical College of Fudan University, Shanghai 200031, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003072:Cognition Disorders / Q000150:complications / Q000473:pathology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004777:Environment; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000378:metabolism; D008738:Methyl Ethers / Q000009:adverse effects*; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D000077154:Rosiglitazone; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D008738:Methyl Ethers; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077149:Sevoflurane