Evaluation of p21 expression and related autism‐like behavior in Bisphenol‐A exposed offspring of Wistar albino rats

Background Bisphenol A (BPA), an endocrine disruptor, may be involved in the etiology of autism spectrum disorders (ASD); however, the mechanism of neuronal and astrocytic damage remains ambiguous. A possible role of altered expression of p21 in autistic‐like behavior in rat offspring was examined w...

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Veröffentlicht in:Birth defects research 2022-07, Vol.114 (11), p.536-550
Hauptverfasser: Singha, Syna Pervaiz, Memon, Samreen, Bano, Umbreen, Isaac, Amir Derick, Shahani, Muhammad Yaqoob
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container_end_page 550
container_issue 11
container_start_page 536
container_title Birth defects research
container_volume 114
creator Singha, Syna Pervaiz
Memon, Samreen
Bano, Umbreen
Isaac, Amir Derick
Shahani, Muhammad Yaqoob
description Background Bisphenol A (BPA), an endocrine disruptor, may be involved in the etiology of autism spectrum disorders (ASD); however, the mechanism of neuronal and astrocytic damage remains ambiguous. A possible role of altered expression of p21 in autistic‐like behavior in rat offspring was examined with prenatal and postnatal BPA exposure. Methods Wistar albino dams were exposed to BPA (5 mg/kg) intraperitoneally throughout pregnancy and until the third postnatal day (PND). Pups were examined on 21st PND for behavioral test. Blood samples were collected for serum lactate levels and pups were sacrificed. Right frontal cortices were dissected out and processed for H&E, immunohistochemical analysis, and gene expression. Results Anxiety like behavior and thigmotaxis along with reduction in serum lactate concentrations were observed in pups exposed to BPA. Decline in neuronal number and decreased astrocytic population with reduced dendritic spines were revealed by H&E and immunohistochemical analysis, respectively, in right frontal cortices. Over expression of p21 was also detected in BPA‐exposed offspring. Conclusions Over expression of p21 may be associated with autistic behavior. Further studies are recommended to explore the structural alterations in other white matter pathways in frontal cortices.
doi_str_mv 10.1002/bdr2.2022
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A possible role of altered expression of p21 in autistic‐like behavior in rat offspring was examined with prenatal and postnatal BPA exposure. Methods Wistar albino dams were exposed to BPA (5 mg/kg) intraperitoneally throughout pregnancy and until the third postnatal day (PND). Pups were examined on 21st PND for behavioral test. Blood samples were collected for serum lactate levels and pups were sacrificed. Right frontal cortices were dissected out and processed for H&amp;E, immunohistochemical analysis, and gene expression. Results Anxiety like behavior and thigmotaxis along with reduction in serum lactate concentrations were observed in pups exposed to BPA. Decline in neuronal number and decreased astrocytic population with reduced dendritic spines were revealed by H&amp;E and immunohistochemical analysis, respectively, in right frontal cortices. Over expression of p21 was also detected in BPA‐exposed offspring. Conclusions Over expression of p21 may be associated with autistic behavior. Further studies are recommended to explore the structural alterations in other white matter pathways in frontal cortices.</description><identifier>ISSN: 2472-1727</identifier><identifier>EISSN: 2472-1727</identifier><identifier>DOI: 10.1002/bdr2.2022</identifier><identifier>PMID: 35560535</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley &amp; Sons, Inc</publisher><subject>albino rat ; astrocyte–neuron lactate shuttle ; Autism ; Bisphenol A ; cellular senescence ; cognitive functions ; Cyclin-dependent kinase inhibitor p21 ; Dendritic spines ; Etiology ; Exposure ; Gene expression ; Juveniles ; Lactic acid ; Offspring ; p21‐activated kinases ; Prenatal experience ; Substantia alba ; Thigmotaxis</subject><ispartof>Birth defects research, 2022-07, Vol.114 (11), p.536-550</ispartof><rights>2022 Wiley Periodicals LLC.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2832-ff25902d3e495022a0cf903d25d8d3f04298b6ce72bd39919a25f3a97205ee723</citedby><cites>FETCH-LOGICAL-c2832-ff25902d3e495022a0cf903d25d8d3f04298b6ce72bd39919a25f3a97205ee723</cites><orcidid>0000-0003-4538-2543</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbdr2.2022$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbdr2.2022$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35560535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Singha, Syna Pervaiz</creatorcontrib><creatorcontrib>Memon, Samreen</creatorcontrib><creatorcontrib>Bano, Umbreen</creatorcontrib><creatorcontrib>Isaac, Amir Derick</creatorcontrib><creatorcontrib>Shahani, Muhammad Yaqoob</creatorcontrib><title>Evaluation of p21 expression and related autism‐like behavior in Bisphenol‐A exposed offspring of Wistar albino rats</title><title>Birth defects research</title><addtitle>Birth Defects Res</addtitle><description>Background Bisphenol A (BPA), an endocrine disruptor, may be involved in the etiology of autism spectrum disorders (ASD); however, the mechanism of neuronal and astrocytic damage remains ambiguous. A possible role of altered expression of p21 in autistic‐like behavior in rat offspring was examined with prenatal and postnatal BPA exposure. Methods Wistar albino dams were exposed to BPA (5 mg/kg) intraperitoneally throughout pregnancy and until the third postnatal day (PND). Pups were examined on 21st PND for behavioral test. Blood samples were collected for serum lactate levels and pups were sacrificed. Right frontal cortices were dissected out and processed for H&amp;E, immunohistochemical analysis, and gene expression. Results Anxiety like behavior and thigmotaxis along with reduction in serum lactate concentrations were observed in pups exposed to BPA. Decline in neuronal number and decreased astrocytic population with reduced dendritic spines were revealed by H&amp;E and immunohistochemical analysis, respectively, in right frontal cortices. Over expression of p21 was also detected in BPA‐exposed offspring. Conclusions Over expression of p21 may be associated with autistic behavior. 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A possible role of altered expression of p21 in autistic‐like behavior in rat offspring was examined with prenatal and postnatal BPA exposure. Methods Wistar albino dams were exposed to BPA (5 mg/kg) intraperitoneally throughout pregnancy and until the third postnatal day (PND). Pups were examined on 21st PND for behavioral test. Blood samples were collected for serum lactate levels and pups were sacrificed. Right frontal cortices were dissected out and processed for H&amp;E, immunohistochemical analysis, and gene expression. Results Anxiety like behavior and thigmotaxis along with reduction in serum lactate concentrations were observed in pups exposed to BPA. Decline in neuronal number and decreased astrocytic population with reduced dendritic spines were revealed by H&amp;E and immunohistochemical analysis, respectively, in right frontal cortices. Over expression of p21 was also detected in BPA‐exposed offspring. 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subjects albino rat
astrocyte–neuron lactate shuttle
Autism
Bisphenol A
cellular senescence
cognitive functions
Cyclin-dependent kinase inhibitor p21
Dendritic spines
Etiology
Exposure
Gene expression
Juveniles
Lactic acid
Offspring
p21‐activated kinases
Prenatal experience
Substantia alba
Thigmotaxis
title Evaluation of p21 expression and related autism‐like behavior in Bisphenol‐A exposed offspring of Wistar albino rats
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