title: Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.
abstract: Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Foquan
authors.identifier: http://orcid.org/0000-0003-0106-0710
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.|Department of Anesthesiology, Jiangxi Province Traditional Chinese Medicine Hospital, Nanchang 33006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Weilu
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA, 22908, United States of America.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Yunlin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Jiangxi Province Tumor Hospital, Nanchang 330006, China.
authors.forename: Binda
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Jiangxi Province Tumor Hospital, Nanchang 330006, China.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, Nanchang University, Nanchang 33006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D005260:Female; D056464:Histone Deacetylase 2 / Q000235:genetics*; D007530:Isoflurane / Q000009:adverse effects*; D018811:Maternal Exposure / Q000009:adverse effects*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D056464:Histone Deacetylase 2