Evaluation of antibiotic-induced behavioral changes in mice

Kwon, Hye-Joo; Mohammed, Afrah E.; Eltom, Kamal H.; Albrahim, Jehan S.; Alburae, Najla Ali

doi:10.1016/j.physbeh.2020.113015

Cited by 13 publications

(9 citation statements)

References 52 publications

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“…Because behavioral changes mediated by antibiotics often correlate with dysfunction of various blood-tissue barriers permeability ( Kwon H. et al, 2020 ; Ray et al, 2021 ), we tested next the integrity of the intestinal barrier and blood-brain barrier (BBB) using the Evans blue (EB) leakage assay. It was detected that offspring born from the 2-w antibiotics group of dams had 2.45 times more EB concentration in the ileum tissue than those of the control group ( p < 0.05; Supplementary Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

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

Shepilov,

Osadchenko,

Kovalenko

et al. 2023

Front. Cell. Neurosci.

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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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Section: Resultsmentioning

confidence: 99%

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

Shepilov,

Osadchenko,

Kovalenko

et al. 2023

Front. Cell. Neurosci.

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show abstract

“…Although sex-dependent, central nervous system-related differences in response of animals to treatment with antibiotics were not – to our knowledge - described previously, indications of changed behaviors after antibiotic therapy were reported recently. Namely, it was showed that administration of clindamycin and/or amoxicillin caused severe behavioral disturbances ( 25 ). First of all, a deterioration of cognitive processes in the novel object recognition test and an increase in the percentage of depressive behavior episodes were noted in the tail suspension test.…”

Section: Discussionmentioning

confidence: 99%

Sex-dependent differences in behavioral and immunological responses to antibiotic and bacteriophage administration in mice

et al. 2023

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IntroductionThe problem of antibiotic resistance is a global one, involving many industries and entailing huge financial outlays. Therefore, the search for alternative methods to combat drug-resistant bacteria has a priority status. Great potential is seen in bacteriophages which have the natural ability to kill bacterial cells. Bacteriophages also have several advantages over antibiotics. Firstly, they are considered ecologically safe (harmless to humans, plants and animals). Secondly, bacteriophages preparations are readily producible and easy to apply. However, before bacteriophages can be authorized for medical and veterinary use, they must be accurately characterized in vitro and in vivo to determinate safety.MethodsTherefore, the aim of this study was to verify for the first time the behavioral and immunological responses of both male and female mice (C57BL/6J) to bacteriophage cocktail, composed of two bacteriophages, and to two commonly used antibiotics, enrofloxacin and tetracycline. Animal behavior, the percentage of lymphocyte populations and subpopulations, cytokine concentrations, blood hematological parameters, gastrointestinal microbiome analysis and the size of internal organs, were evaluated.ResultsUnexpectedly, we observed a sex-dependent, negative effect of antibiotic therapy, which not only involved the functioning of the immune system, but could also significantly impaired the activity of the central nervous system, as manifested by disruption of the behavioral pattern, especially exacerbated in females. In contrast to antibiotics, complex behavioral and immunological analyses confirmed the lack of adverse effects during the bacteriophage cocktail administration.DiscussionThe mechanism of the differences between males and females in appearance of adverse effects, related to the behavioral and immune functions, in the response to antibiotic treatment remains to be elucidated. One might imagine that differences in hormones and/or different permeability of the blood-brain barrier can be important factors, however, extensive studies are required to find the real reason(s).

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“…24 Antibiotics are known to alter the gut bacterial composition, including inhibiting the abundance of Akkermansia. 47 Antibiotics perturb community richness, deplete the abundance of specific bacteria, reduce memory, 48 and modulate metabolite profiles. 49 In this study, no difference was found in memory and serum taurine levels between the control + antibiotic group and the AGIQ + antibiotic group.…”

Section: ■ Discussionmentioning

confidence: 99%

Potential Effects of Alpha-Glycosyl Isoquercitrin on Memory by Altering the Gut Microbiota-Blood–Brain Axis in Mice

Liu,

Inoue,

Koyanagi

et al. 2023

J. Agric. Food Chem.

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Alpha-glycosyl isoquercitrin (AGIQ), composed of isoquercitrin and glycosylated quercetin, has multiple biological effects. Here, we further examined the influence of AGIQ on brain function and provided its potential mechanism. Male C57BL/6 mice were treated with 0, 0.005, and 0.05% AGIQ in drinking water for 4 weeks prior to behavioral testing. Behavior tests showed that 0.05% AGIQ treatment significantly improved learning and memory function without affecting emotion. In the hippocampus, the gene expression of antioxidative defense enzymes was upregulated after 0.05% AGIQ treatment. In contrast, AGIQ caused significant alterations in the microbial abundance of genera Akkermansia, Bifidobacterium, and Alistipes associated with memory function. Metabolomics analysis identified that taurine concentration was significantly increased in serum and hippocampus from AGIQ-treated mice. The correlation analysis suggested that elevated serum taurine levels were closely related to the abundance of Akkermansia, indicating the underlying crosstalk of gut microbiota and serum metabolites. In vitro fecal culture further demonstrated that AGIQ could increase the level of Akkermansia. Taurine could exert antioxidant activity in SH-SY5Y neuroblastoma cell lines in vitro. Finally, vancomycin-induced alterations of gut microbiota attenuated the taurine increases in the serum and the antioxidant gene level in the hippocampus by AGIQ. Taken together, it is likely that AGIQ could increase genus Akkermansia abundance and ultimately increase taurine levels in serum and hippocampus to improve learning and memory function, relying on the gut microbiota-blood−brain axis. Our results supply a new view for understanding effects of AGIQ on brain function.

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Evaluation of antibiotic-induced behavioral changes in mice

Cited by 13 publications

References 52 publications

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

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

Sex-dependent differences in behavioral and immunological responses to antibiotic and bacteriophage administration in mice

Potential Effects of Alpha-Glycosyl Isoquercitrin on Memory by Altering the Gut Microbiota-Blood–Brain Axis in Mice

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