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Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring

Maternal antibiotics administration (MAA) is among the widely used therapeutic approaches in pregnancy. Although published evidence demonstrates that infants exposed to antibiotics immediately after birth have altered recognition memory responses at one month of age, very little is known about in ut...

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Autores principales: Shepilov, Dmytro, Osadchenko, Iryna, Kovalenko, Tetiana, Yamada, Chiaki, Chereshynska, Anastasiia, Smozhanyk, Kateryna, Ostrovska, Galyna, Groppa, Stanislav, Movila, Alexandru, Skibo, Galyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206017/
https://www.ncbi.nlm.nih.gov/pubmed/37234915
http://dx.doi.org/10.3389/fncel.2023.1176676
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author Shepilov, Dmytro
Osadchenko, Iryna
Kovalenko, Tetiana
Yamada, Chiaki
Chereshynska, Anastasiia
Smozhanyk, Kateryna
Ostrovska, Galyna
Groppa, Stanislav
Movila, Alexandru
Skibo, Galyna
author_facet Shepilov, Dmytro
Osadchenko, Iryna
Kovalenko, Tetiana
Yamada, Chiaki
Chereshynska, Anastasiia
Smozhanyk, Kateryna
Ostrovska, Galyna
Groppa, Stanislav
Movila, Alexandru
Skibo, Galyna
author_sort Shepilov, Dmytro
collection PubMed
description Maternal antibiotics administration (MAA) is among the widely used therapeutic approaches in pregnancy. Although published evidence demonstrates that infants exposed to antibiotics immediately after birth have altered recognition memory responses at one month of age, very little is known about in utero effects of antibiotics on the neuronal function and behavior of children after birth. Therefore, this study aimed to evaluate the impact of MAA at different periods of pregnancy on memory decline and brain structural alterations in young mouse offspring after their first month of life. To study the effects of MAA on 4-week-old offspring, pregnant C57BL/6J mouse dams (2–3-month-old; n = 4/group) were exposed to a cocktail of amoxicillin (205 mg/kg/day) and azithromycin (51 mg/kg/day) in sterile drinking water (daily/1 week) during either the 2nd or 3rd week of pregnancy and stopped after delivery. A control group of pregnant dams was exposed to sterile drinking water alone during all three weeks of pregnancy. Then, the 4-week-old offspring mice were first evaluated for behavioral changes. Using the Morris water maze assay, we revealed that exposure of pregnant mice to antibiotics at the 2nd and 3rd weeks of pregnancy significantly altered spatial reference memory and learning skills in their offspring compared to those delivered from the control group of dams. In contrast, no significant difference in long-term associative memory was detected between offspring groups using the novel object recognition test. Then, we histologically evaluated brain samples from the same offspring individuals using conventional immunofluorescence and electron microscopy assays. To our knowledge, we observed a reduction in the density of the hippocampal CA1 pyramidal neurons and hypomyelination in the corpus callosum in groups of mice in utero exposed to antibiotics at the 2nd and 3rd weeks of gestation. In addition, offspring exposed to antibiotics at the 2nd or 3rd week of gestation demonstrated a decreased astrocyte cell surface area and astrocyte territories or depletion of neurogenesis in the dentate gyrus and hippocampal synaptic loss, respectively. Altogether, this study shows that MAA at different times of pregnancy can pathologically alter cognitive behavior and brain development in offspring at an early age after weaning.
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spelling pubmed-102060172023-05-25 Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring Shepilov, Dmytro Osadchenko, Iryna Kovalenko, Tetiana Yamada, Chiaki Chereshynska, Anastasiia Smozhanyk, Kateryna Ostrovska, Galyna Groppa, Stanislav Movila, Alexandru Skibo, Galyna Front Cell Neurosci Neuroscience Maternal antibiotics administration (MAA) is among the widely used therapeutic approaches in pregnancy. Although published evidence demonstrates that infants exposed to antibiotics immediately after birth have altered recognition memory responses at one month of age, very little is known about in utero effects of antibiotics on the neuronal function and behavior of children after birth. Therefore, this study aimed to evaluate the impact of MAA at different periods of pregnancy on memory decline and brain structural alterations in young mouse offspring after their first month of life. To study the effects of MAA on 4-week-old offspring, pregnant C57BL/6J mouse dams (2–3-month-old; n = 4/group) were exposed to a cocktail of amoxicillin (205 mg/kg/day) and azithromycin (51 mg/kg/day) in sterile drinking water (daily/1 week) during either the 2nd or 3rd week of pregnancy and stopped after delivery. A control group of pregnant dams was exposed to sterile drinking water alone during all three weeks of pregnancy. Then, the 4-week-old offspring mice were first evaluated for behavioral changes. Using the Morris water maze assay, we revealed that exposure of pregnant mice to antibiotics at the 2nd and 3rd weeks of pregnancy significantly altered spatial reference memory and learning skills in their offspring compared to those delivered from the control group of dams. In contrast, no significant difference in long-term associative memory was detected between offspring groups using the novel object recognition test. Then, we histologically evaluated brain samples from the same offspring individuals using conventional immunofluorescence and electron microscopy assays. To our knowledge, we observed a reduction in the density of the hippocampal CA1 pyramidal neurons and hypomyelination in the corpus callosum in groups of mice in utero exposed to antibiotics at the 2nd and 3rd weeks of gestation. In addition, offspring exposed to antibiotics at the 2nd or 3rd week of gestation demonstrated a decreased astrocyte cell surface area and astrocyte territories or depletion of neurogenesis in the dentate gyrus and hippocampal synaptic loss, respectively. Altogether, this study shows that MAA at different times of pregnancy can pathologically alter cognitive behavior and brain development in offspring at an early age after weaning. Frontiers Media S.A. 2023-05-10 /pmc/articles/PMC10206017/ /pubmed/37234915 http://dx.doi.org/10.3389/fncel.2023.1176676 Text en Copyright © 2023 Shepilov, Osadchenko, Kovalenko, Yamada, Chereshynska, Smozhanyk, Ostrovska, Groppa, Movila and Skibo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shepilov, Dmytro
Osadchenko, Iryna
Kovalenko, Tetiana
Yamada, Chiaki
Chereshynska, Anastasiia
Smozhanyk, Kateryna
Ostrovska, Galyna
Groppa, Stanislav
Movila, Alexandru
Skibo, Galyna
Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
title Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
title_full Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
title_fullStr Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
title_full_unstemmed Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
title_short Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
title_sort maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206017/
https://www.ncbi.nlm.nih.gov/pubmed/37234915
http://dx.doi.org/10.3389/fncel.2023.1176676
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