title: Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment.
abstract: Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at ≥P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane-induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities.
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Mu-Huo
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Zhong-Yun
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Qiu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Guang-Fen
authors.initials: GF
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Yong G
authors.initials: YG
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China. yjyangjj@126.com.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000473:pathology*; D004777:Environment; D007395:Interneurons / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000009:adverse effects*; D008810:Mice, Inbred C57BL; D010320:Parvalbumins / Q000378:metabolism*; D000077149:Sevoflurane
chemical_list: D008738:Methyl Ethers; D010320:Parvalbumins; D000077149:Sevoflurane
keywords: Cognition; Enriched environment; Parvalbumin; Sevoflurane