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.

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 e...

Full description

Bibliographic Details
Main Authors: Foquan Luo, Yan Hu, Weilu Zhao, Zhiyi Zuo, Qi Yu, Zhiyi Liu, Jiamei Lin, Yunlin Feng, Binda Li, Liuqin Wu, Lin Xu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4990207?pdf=render
id doaj-fb07354041844446a47b3245af15c014
record_format Article
spelling doaj-fb07354041844446a47b3245af15c0142020-11-24T22:03:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e016082610.1371/journal.pone.0160826Maternal 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.Foquan LuoYan HuWeilu ZhaoZhiyi ZuoQi YuZhiyi LiuJiamei LinYunlin FengBinda LiLiuqin WuLin XuIncreasing 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.http://europepmc.org/articles/PMC4990207?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Foquan Luo
Yan Hu
Weilu Zhao
Zhiyi Zuo
Qi Yu
Zhiyi Liu
Jiamei Lin
Yunlin Feng
Binda Li
Liuqin Wu
Lin Xu
spellingShingle Foquan Luo
Yan Hu
Weilu Zhao
Zhiyi Zuo
Qi Yu
Zhiyi Liu
Jiamei Lin
Yunlin Feng
Binda Li
Liuqin Wu
Lin Xu
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.
PLoS ONE
author_facet Foquan Luo
Yan Hu
Weilu Zhao
Zhiyi Zuo
Qi Yu
Zhiyi Liu
Jiamei Lin
Yunlin Feng
Binda Li
Liuqin Wu
Lin Xu
author_sort Foquan Luo
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.
title_short 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_sort 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.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2016-01-01
description 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.
url http://europepmc.org/articles/PMC4990207?pdf=render
work_keys_str_mv AT foquanluo maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT yanhu maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT weiluzhao maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT zhiyizuo maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT qiyu maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT zhiyiliu maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT jiameilin maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT yunlinfeng maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT bindali maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT liuqinwu maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
AT linxu maternalexposureofratstoisofluraneduringlatepregnancyimpairsspatiallearningandmemoryintheoffspringbyupregulatingtheexpressionofhistonedeacetylase2
_version_ 1725831949202751488