Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability
Ketamine exposure can lead to selective neuroapoptosis in the developing brain. p66ShcA, the cellular adapter protein expressed selectively in immature neurons, is a known pro-apoptotic molecule that triggers neuroapoptosis when activated. Sprague-Dawley rats at postnatal day 7 were subcutaneously i...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wolters Kluwer Medknow Publications
2020-01-01
|
Series: | Neural Regeneration Research |
Subjects: | |
Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=5;spage=880;epage=886;aulast=Lyu |
id |
doaj-b3efea92bdc74d27ac658cb69400383c |
---|---|
record_format |
Article |
spelling |
doaj-b3efea92bdc74d27ac658cb69400383c2020-11-25T02:10:10ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742020-01-0115588088610.4103/1673-5374.268929Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning abilityDan LyuNing TangAndrew W WomackYong-Jin HeQing LinKetamine exposure can lead to selective neuroapoptosis in the developing brain. p66ShcA, the cellular adapter protein expressed selectively in immature neurons, is a known pro-apoptotic molecule that triggers neuroapoptosis when activated. Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg, six times at 2-hour intervals. At 0, 1, 3, and 6 hours after final injection, western blot assay was used to detect the expression of cleaved caspase-3, p66ShcA, and phosphorylated p66ShcA. We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours. The same procedure was performed on a different group of rats. At the age of 4 weeks, spatial learning and memory abilities were tested with the Morris water maze. Latency to find the hidden platform for these rats was longer than it was for control rats, although the residence time in the target quadrant was similar. These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period. This may have contributed to the deficit in spatial learning and memory that persisted into adulthood. The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington, USA (approval No. A13.008) on January 22, 2013.http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=5;spage=880;epage=886;aulast=Lyucaspase-3; developmental neuroapoptosis; hippocampus; ketamine; morris water maze; n-methyl-d-aspartate acid receptors; p66shca; spatial learning |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dan Lyu Ning Tang Andrew W Womack Yong-Jin He Qing Lin |
spellingShingle |
Dan Lyu Ning Tang Andrew W Womack Yong-Jin He Qing Lin Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability Neural Regeneration Research caspase-3; developmental neuroapoptosis; hippocampus; ketamine; morris water maze; n-methyl-d-aspartate acid receptors; p66shca; spatial learning |
author_facet |
Dan Lyu Ning Tang Andrew W Womack Yong-Jin He Qing Lin |
author_sort |
Dan Lyu |
title |
Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability |
title_short |
Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability |
title_full |
Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability |
title_fullStr |
Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability |
title_full_unstemmed |
Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability |
title_sort |
neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability |
publisher |
Wolters Kluwer Medknow Publications |
series |
Neural Regeneration Research |
issn |
1673-5374 |
publishDate |
2020-01-01 |
description |
Ketamine exposure can lead to selective neuroapoptosis in the developing brain. p66ShcA, the cellular adapter protein expressed selectively in immature neurons, is a known pro-apoptotic molecule that triggers neuroapoptosis when activated. Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg, six times at 2-hour intervals. At 0, 1, 3, and 6 hours after final injection, western blot assay was used to detect the expression of cleaved caspase-3, p66ShcA, and phosphorylated p66ShcA. We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours. The same procedure was performed on a different group of rats. At the age of 4 weeks, spatial learning and memory abilities were tested with the Morris water maze. Latency to find the hidden platform for these rats was longer than it was for control rats, although the residence time in the target quadrant was similar. These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period. This may have contributed to the deficit in spatial learning and memory that persisted into adulthood. The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington, USA (approval No. A13.008) on January 22, 2013. |
topic |
caspase-3; developmental neuroapoptosis; hippocampus; ketamine; morris water maze; n-methyl-d-aspartate acid receptors; p66shca; spatial learning |
url |
http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=5;spage=880;epage=886;aulast=Lyu |
work_keys_str_mv |
AT danlyu neonatalketamineexposureinducedhippocampalneuroapoptosisinthedevelopingbrainimpairsadultspatiallearningability AT ningtang neonatalketamineexposureinducedhippocampalneuroapoptosisinthedevelopingbrainimpairsadultspatiallearningability AT andrewwwomack neonatalketamineexposureinducedhippocampalneuroapoptosisinthedevelopingbrainimpairsadultspatiallearningability AT yongjinhe neonatalketamineexposureinducedhippocampalneuroapoptosisinthedevelopingbrainimpairsadultspatiallearningability AT qinglin neonatalketamineexposureinducedhippocampalneuroapoptosisinthedevelopingbrainimpairsadultspatiallearningability |
_version_ |
1724920351280857088 |