Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.

Epidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS) model of immune activation in rats, the offspring exhibit significant impairments in behavio...

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Main Authors: Moogeh Baharnoori, Sanjeev K Bhardwaj, Lalit K Srivastava
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3547943?pdf=render
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author Moogeh Baharnoori
Sanjeev K Bhardwaj
Lalit K Srivastava
author_facet Moogeh Baharnoori
Sanjeev K Bhardwaj
Lalit K Srivastava
author_sort Moogeh Baharnoori
collection DOAJ
description Epidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS) model of immune activation in rats, the offspring exhibit significant impairments in behaviors mediated by central dopamine (DA) system. This study aimed to examine the temporal and regional pattern of postnatal DA development in the male offspring of pregnant Sprague-Dawley rats administered with 100 µg/kg LPS or saline at gestational days 15/16. Using ligand autoradiography, D1 and D2 dopamine receptors (D1R, D2R) and dopamine transporter (DAT) binding levels were measured in the prefrontal cortex (PFC) and sub cortical regions (dorsal striatum and nucleus accumbens core and shell) at pre pubertal (P35) and post pubertal ages (P60). We found a significant decrease in D2R ligand [(3)H] YM-90151-2 binding in the medial PFC (mPFC) in prenatal LPS-treated animals at P35 and P60 compared to respective saline groups. The decrease in D2R levels was not observed in the striatum or accumbens of maternal LPS-treated animals. No significant changes were observed in [(3)H] SCH23390 binding to D1R. However, the level of [(125)I] RTI-121 binding to DAT was selectively reduced in the nucleus accumbens core and shell at P35 in the prenatal LPS group. Immunohistochemical analysis showed that number of D2R immunopositive cells in infralimbic/prelimbic (IL/PL) part of mPFC was significantly reduced in the LPS group at P60. Prenatal LPS treatment did not significantly affect either the total number of mature neurons or parvalbumin (PV)-immunopositive interneurons in this region. However the number of PV and D2R co-labeled neurons was significantly reduced in the IL/PL subregion of PFC of LPS treated animals. Our data suggests D2R deficit in the PFC and PV interneurons may be relevant to understanding mechanisms of cortical dysfunctions described in prenatal infection animal models as well as schizophrenia.
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spelling doaj.art-c2e789579ed347498fa8308f9cce34e22022-12-22T01:23:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5443910.1371/journal.pone.0054439Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.Moogeh BaharnooriSanjeev K BhardwajLalit K SrivastavaEpidemiological evidence supports that maternal infection during gestation are notable risk factors for developmental mental illnesses including schizophrenia and autism. In prenatal lipopolysaccharide (LPS) model of immune activation in rats, the offspring exhibit significant impairments in behaviors mediated by central dopamine (DA) system. This study aimed to examine the temporal and regional pattern of postnatal DA development in the male offspring of pregnant Sprague-Dawley rats administered with 100 µg/kg LPS or saline at gestational days 15/16. Using ligand autoradiography, D1 and D2 dopamine receptors (D1R, D2R) and dopamine transporter (DAT) binding levels were measured in the prefrontal cortex (PFC) and sub cortical regions (dorsal striatum and nucleus accumbens core and shell) at pre pubertal (P35) and post pubertal ages (P60). We found a significant decrease in D2R ligand [(3)H] YM-90151-2 binding in the medial PFC (mPFC) in prenatal LPS-treated animals at P35 and P60 compared to respective saline groups. The decrease in D2R levels was not observed in the striatum or accumbens of maternal LPS-treated animals. No significant changes were observed in [(3)H] SCH23390 binding to D1R. However, the level of [(125)I] RTI-121 binding to DAT was selectively reduced in the nucleus accumbens core and shell at P35 in the prenatal LPS group. Immunohistochemical analysis showed that number of D2R immunopositive cells in infralimbic/prelimbic (IL/PL) part of mPFC was significantly reduced in the LPS group at P60. Prenatal LPS treatment did not significantly affect either the total number of mature neurons or parvalbumin (PV)-immunopositive interneurons in this region. However the number of PV and D2R co-labeled neurons was significantly reduced in the IL/PL subregion of PFC of LPS treated animals. Our data suggests D2R deficit in the PFC and PV interneurons may be relevant to understanding mechanisms of cortical dysfunctions described in prenatal infection animal models as well as schizophrenia.http://europepmc.org/articles/PMC3547943?pdf=render
spellingShingle Moogeh Baharnoori
Sanjeev K Bhardwaj
Lalit K Srivastava
Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.
PLoS ONE
title Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.
title_full Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.
title_fullStr Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.
title_full_unstemmed Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.
title_short Effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring.
title_sort effect of maternal lipopolysaccharide administration on the development of dopaminergic receptors and transporter in the rat offspring
url http://europepmc.org/articles/PMC3547943?pdf=render
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AT lalitksrivastava effectofmaternallipopolysaccharideadministrationonthedevelopmentofdopaminergicreceptorsandtransporterintheratoffspring