Cargando…

Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice

Acetaminophen (N-acetyl-p-aminophenol (APAP), also known as paracetamol) is one of the most common medications used by the general population, including pregnant people. Although many human observational and animal model studies have shown associations between prenatal and early postnatal APAP expos...

Descripción completa

Detalles Bibliográficos
Autores principales: Baker, Brennan H., Rafikian, Elizabeth E., Hamblin, Paul B., Strait, Madeleine D., Yang, Mu, Pearson, Brandon L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940030/
https://www.ncbi.nlm.nih.gov/pubmed/36549432
http://dx.doi.org/10.1016/j.nbd.2022.105970
_version_ 1784890995137052672
author Baker, Brennan H.
Rafikian, Elizabeth E.
Hamblin, Paul B.
Strait, Madeleine D.
Yang, Mu
Pearson, Brandon L.
author_facet Baker, Brennan H.
Rafikian, Elizabeth E.
Hamblin, Paul B.
Strait, Madeleine D.
Yang, Mu
Pearson, Brandon L.
author_sort Baker, Brennan H.
collection PubMed
description Acetaminophen (N-acetyl-p-aminophenol (APAP), also known as paracetamol) is one of the most common medications used by the general population, including pregnant people. Although many human observational and animal model studies have shown associations between prenatal and early postnatal APAP exposure and attention deficit hyperactivity disorder, autism spectrum disorders, and altered neurodevelopment, the existing literature is limited. In particular, no mouse studies of prenatal APAP exposure have investigated offspring attention deficits in behavioral tasks specifically designed to measure attention, and no prior rodent studies have utilized ‘omics’ technologies, such as transcriptomics, for an untargeted exploration of potential mechanisms. We randomly assigned pregnant mice (starting embryonic day 4–10) to receive APAP (150 mg/kg/day) or vehicle control through postnatal day 14. We evaluated 111 mouse offspring in a battery of behavioral tests, including pup ultrasonic vocalizations, elevated plus-maze, open field test, CatWalk (gait), pre-pulse inhibition, and the automated 5-choice serial reaction time task. Prefrontal cortex was collected at birth from 24 pups for RNA sequencing. Developmental APAP treatment resulted in increased and hastened separation-induced pup vocalizations between postnatal days 2 and 11, as well as decreased ambulation and vertical rearings in the open field in male but not female adult offspring. APAP treatment was also associated with altered sex-specific prefrontal cortex gene expression relating to glutathione and cytochrome p450 metabolism, DNA damage, and the endocrine and immune systems. This study provides additional evidence for the neurodevelopmental harm of prenatal APAP exposure and generates hypotheses for underlying molecular pathways via RNA sequencing.
format Online
Article
Text
id pubmed-9940030
institution National Center for Biotechnology Information
language English
publishDate 2023
record_format MEDLINE/PubMed
spelling pubmed-99400302023-02-20 Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice Baker, Brennan H. Rafikian, Elizabeth E. Hamblin, Paul B. Strait, Madeleine D. Yang, Mu Pearson, Brandon L. Neurobiol Dis Article Acetaminophen (N-acetyl-p-aminophenol (APAP), also known as paracetamol) is one of the most common medications used by the general population, including pregnant people. Although many human observational and animal model studies have shown associations between prenatal and early postnatal APAP exposure and attention deficit hyperactivity disorder, autism spectrum disorders, and altered neurodevelopment, the existing literature is limited. In particular, no mouse studies of prenatal APAP exposure have investigated offspring attention deficits in behavioral tasks specifically designed to measure attention, and no prior rodent studies have utilized ‘omics’ technologies, such as transcriptomics, for an untargeted exploration of potential mechanisms. We randomly assigned pregnant mice (starting embryonic day 4–10) to receive APAP (150 mg/kg/day) or vehicle control through postnatal day 14. We evaluated 111 mouse offspring in a battery of behavioral tests, including pup ultrasonic vocalizations, elevated plus-maze, open field test, CatWalk (gait), pre-pulse inhibition, and the automated 5-choice serial reaction time task. Prefrontal cortex was collected at birth from 24 pups for RNA sequencing. Developmental APAP treatment resulted in increased and hastened separation-induced pup vocalizations between postnatal days 2 and 11, as well as decreased ambulation and vertical rearings in the open field in male but not female adult offspring. APAP treatment was also associated with altered sex-specific prefrontal cortex gene expression relating to glutathione and cytochrome p450 metabolism, DNA damage, and the endocrine and immune systems. This study provides additional evidence for the neurodevelopmental harm of prenatal APAP exposure and generates hypotheses for underlying molecular pathways via RNA sequencing. 2023-02 2022-12-19 /pmc/articles/PMC9940030/ /pubmed/36549432 http://dx.doi.org/10.1016/j.nbd.2022.105970 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Baker, Brennan H.
Rafikian, Elizabeth E.
Hamblin, Paul B.
Strait, Madeleine D.
Yang, Mu
Pearson, Brandon L.
Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
title Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
title_full Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
title_fullStr Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
title_full_unstemmed Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
title_short Sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
title_sort sex-specific neurobehavioral and prefrontal cortex gene expression alterations following developmental acetaminophen exposure in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940030/
https://www.ncbi.nlm.nih.gov/pubmed/36549432
http://dx.doi.org/10.1016/j.nbd.2022.105970
work_keys_str_mv AT bakerbrennanh sexspecificneurobehavioralandprefrontalcortexgeneexpressionalterationsfollowingdevelopmentalacetaminophenexposureinmice
AT rafikianelizabethe sexspecificneurobehavioralandprefrontalcortexgeneexpressionalterationsfollowingdevelopmentalacetaminophenexposureinmice
AT hamblinpaulb sexspecificneurobehavioralandprefrontalcortexgeneexpressionalterationsfollowingdevelopmentalacetaminophenexposureinmice
AT straitmadeleined sexspecificneurobehavioralandprefrontalcortexgeneexpressionalterationsfollowingdevelopmentalacetaminophenexposureinmice
AT yangmu sexspecificneurobehavioralandprefrontalcortexgeneexpressionalterationsfollowingdevelopmentalacetaminophenexposureinmice
AT pearsonbrandonl sexspecificneurobehavioralandprefrontalcortexgeneexpressionalterationsfollowingdevelopmentalacetaminophenexposureinmice