Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice

Abstract Exposure to antibiotic treatment has been associated with increased vulnerability to various psychiatric disorders. However, a research gap exists in understanding how adolescent antibiotic therapy affects behavior and cognition. Many antibiotics that target bacterial translation may also a...

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Autores principales:	Anouk C. Tengeler, Tim L. Emmerzaal, Bram Geenen, Vivienne Verweij, Miranda van Bodegom, Eva Morava, Amanda J. Kiliaan, Tamas Kozicz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dad546a0d8e34a448409e01707e3e61c
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spelling	oai:doaj.org-article:dad546a0d8e34a448409e01707e3e61c2021-12-02T17:23:51ZEarly-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice10.1038/s41598-021-92203-12045-2322https://doaj.org/article/dad546a0d8e34a448409e01707e3e61c2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92203-1https://doaj.org/toc/2045-2322Abstract Exposure to antibiotic treatment has been associated with increased vulnerability to various psychiatric disorders. However, a research gap exists in understanding how adolescent antibiotic therapy affects behavior and cognition. Many antibiotics that target bacterial translation may also affect mitochondrial translation resulting in impaired mitochondrial function. The brain is one of the most metabolically active organs, and hence is the most vulnerable to impaired mitochondrial function. We hypothesized that exposure to antibiotics during early adolescence would directly affect brain mitochondrial function, and result in altered behavior and cognition. We administered amoxicillin, chloramphenicol, or gentamicin in the drinking water to young adolescent male wild-type mice. Next, we assayed mitochondrial oxidative phosphorylation complex activities in the cerebral cortex, performed behavioral screening and targeted mass spectrometry-based acylcarnitine profiling in the cerebral cortex. We found that mice exposed to chloramphenicol showed increased repetitive and compulsive-like behavior in the marble burying test, an accurate and sensitive assay of anxiety, concomitant with decreased mitochondrial complex IV activity. Our results suggest that only adolescent chloramphenicol exposure leads to impaired brain mitochondrial complex IV function, and could therefore be a candidate driver event for increased anxiety-like and repetitive, compulsive-like behaviors.Anouk C. TengelerTim L. EmmerzaalBram GeenenVivienne VerweijMiranda van BodegomEva MoravaAmanda J. KiliaanTamas KoziczNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anouk C. Tengeler Tim L. Emmerzaal Bram Geenen Vivienne Verweij Miranda van Bodegom Eva Morava Amanda J. Kiliaan Tamas Kozicz Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
description	Abstract Exposure to antibiotic treatment has been associated with increased vulnerability to various psychiatric disorders. However, a research gap exists in understanding how adolescent antibiotic therapy affects behavior and cognition. Many antibiotics that target bacterial translation may also affect mitochondrial translation resulting in impaired mitochondrial function. The brain is one of the most metabolically active organs, and hence is the most vulnerable to impaired mitochondrial function. We hypothesized that exposure to antibiotics during early adolescence would directly affect brain mitochondrial function, and result in altered behavior and cognition. We administered amoxicillin, chloramphenicol, or gentamicin in the drinking water to young adolescent male wild-type mice. Next, we assayed mitochondrial oxidative phosphorylation complex activities in the cerebral cortex, performed behavioral screening and targeted mass spectrometry-based acylcarnitine profiling in the cerebral cortex. We found that mice exposed to chloramphenicol showed increased repetitive and compulsive-like behavior in the marble burying test, an accurate and sensitive assay of anxiety, concomitant with decreased mitochondrial complex IV activity. Our results suggest that only adolescent chloramphenicol exposure leads to impaired brain mitochondrial complex IV function, and could therefore be a candidate driver event for increased anxiety-like and repetitive, compulsive-like behaviors.
format	article
author	Anouk C. Tengeler Tim L. Emmerzaal Bram Geenen Vivienne Verweij Miranda van Bodegom Eva Morava Amanda J. Kiliaan Tamas Kozicz
author_facet	Anouk C. Tengeler Tim L. Emmerzaal Bram Geenen Vivienne Verweij Miranda van Bodegom Eva Morava Amanda J. Kiliaan Tamas Kozicz
author_sort	Anouk C. Tengeler
title	Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
title_short	Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
title_full	Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
title_fullStr	Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
title_full_unstemmed	Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
title_sort	early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dad546a0d8e34a448409e01707e3e61c
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Early-adolescent antibiotic exposure results in mitochondrial and behavioral deficits in adult male mice

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