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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1176676/full |
| _version_ | 1827950679566581760 |
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| author | Dmytro Shepilov Iryna Osadchenko Tetiana Kovalenko Chiaki Yamada Chiaki Yamada Anastasiia Chereshynska Kateryna Smozhanyk Galyna Ostrovska Stanislav Groppa Stanislav Groppa Alexandru Movila Alexandru Movila Galyna Skibo |
| author_facet | Dmytro Shepilov Iryna Osadchenko Tetiana Kovalenko Chiaki Yamada Chiaki Yamada Anastasiia Chereshynska Kateryna Smozhanyk Galyna Ostrovska Stanislav Groppa Stanislav Groppa Alexandru Movila Alexandru Movila Galyna Skibo |
| author_sort | Dmytro Shepilov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T13:29:20Z |
| format | Article |
| id | doaj.art-25fb9ba607a44242ac544577464e5708 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-09T13:29:20Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-25fb9ba607a44242ac544577464e57082023-05-10T04:33:48ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-05-011710.3389/fncel.2023.11766761176676Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspringDmytro Shepilov0Iryna Osadchenko1Tetiana Kovalenko2Chiaki Yamada3Chiaki Yamada4Anastasiia Chereshynska5Kateryna Smozhanyk6Galyna Ostrovska7Stanislav Groppa8Stanislav Groppa9Alexandru Movila10Alexandru Movila11Galyna Skibo12Department of Cytology, Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, UkraineDepartment of Cytology, Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, UkraineDepartment of Cytology, Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, UkraineDepartment of Biomedical Sciences and Comprehensive Care, School of Dentistry, Indiana University, Indianapolis, IN, United StatesIndiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Biomedical Sciences and Comprehensive Care, School of Dentistry, Indiana University, Indianapolis, IN, United StatesDepartment of Cytology, Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, UkraineDepartment of Cytology, Histology, and Reproductive Medicine, Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, UkraineDepartment of Neurology, Institute of Emergency Medicine, Chisinau, MoldovaDepartment of Neurology, State University of Medicine and Pharmacy “Nicolae Testemiţanu”, Chisinau, MoldovaDepartment of Biomedical Sciences and Comprehensive Care, School of Dentistry, Indiana University, Indianapolis, IN, United StatesIndiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Cytology, Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, UkraineMaternal 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.https://www.frontiersin.org/articles/10.3389/fncel.2023.1176676/fulloffspring miceantibioticsmemory and learninghippocampal structureneurogenesismyelination |
| spellingShingle | Dmytro Shepilov Iryna Osadchenko Tetiana Kovalenko Chiaki Yamada Chiaki Yamada Anastasiia Chereshynska Kateryna Smozhanyk Galyna Ostrovska Stanislav Groppa Stanislav Groppa Alexandru Movila Alexandru Movila Galyna Skibo Maternal antibiotic administration during gestation can affect the memory and brain structure in mouse offspring Frontiers in Cellular Neuroscience offspring mice antibiotics memory and learning hippocampal structure neurogenesis myelination |
| 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 | offspring mice antibiotics memory and learning hippocampal structure neurogenesis myelination |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1176676/full |
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