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Neuroglia in the autistic brain: evidence from a preclinical model

BACKGROUND: Neuroglial cells that provide homeostatic support and form defence of the nervous system contribute to all neurological disorders. We analyzed three major types of neuroglia, astrocytes, oligodendrocytes, and microglia in the brains of an animal model of autism spectrum disorder, in whic...

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Autores principales: Bronzuoli, Maria Rosanna, Facchinetti, Roberta, Ingrassia, Davide, Sarvadio, Michela, Schiavi, Sara, Steardo, Luca, Verkhratsky, Alexei, Trezza, Viviana, Scuderi, Caterina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307226/
https://www.ncbi.nlm.nih.gov/pubmed/30603062
http://dx.doi.org/10.1186/s13229-018-0254-0
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author Bronzuoli, Maria Rosanna
Facchinetti, Roberta
Ingrassia, Davide
Sarvadio, Michela
Schiavi, Sara
Steardo, Luca
Verkhratsky, Alexei
Trezza, Viviana
Scuderi, Caterina
author_facet Bronzuoli, Maria Rosanna
Facchinetti, Roberta
Ingrassia, Davide
Sarvadio, Michela
Schiavi, Sara
Steardo, Luca
Verkhratsky, Alexei
Trezza, Viviana
Scuderi, Caterina
author_sort Bronzuoli, Maria Rosanna
collection PubMed
description BACKGROUND: Neuroglial cells that provide homeostatic support and form defence of the nervous system contribute to all neurological disorders. We analyzed three major types of neuroglia, astrocytes, oligodendrocytes, and microglia in the brains of an animal model of autism spectrum disorder, in which rats were exposed prenatally to antiepileptic and mood stabilizer drug valproic acid; this model being of acknowledged clinical relevance. METHODS: We tested the autistic-like behaviors of valproic acid-prenatally exposed male rats by performing isolation-induced ultrasonic vocalizations, the three-chamber test, and the hole board test. To account for human infancy, adolescence, and adulthood, such tasks were performed at postnatal day 13, postnatal day 35, and postnatal day 90, respectively. After sacrifice, we examined gene and protein expression of specific markers of neuroglia in hippocampus, prefrontal cortex, and cerebellum, these brain regions being associated with autism spectrum disorder pathogenesis. RESULTS: Infant offspring of VPA-exposed dams emitted less ultrasonic vocalizations when isolated from their mothers and siblings and, in adolescence and adulthood, they showed altered sociability in the three chamber test and increased stereotypic behavior in the hole board test. Molecular analyses indicate that prenatal valproic acid exposure affects all types of neuroglia, mainly causing transcriptional modifications. The most prominent changes occur in prefrontal cortex and in the hippocampus of autistic-like animals; these changes are particularly evident during infancy and adolescence, while they appear to be mitigated in adulthood. CONCLUSIONS: Neuroglial pathological phenotype in autism spectrum disorder rat model appears to be rather mild with little signs of widespread and chronic neuroinflammation.
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spelling pubmed-63072262019-01-02 Neuroglia in the autistic brain: evidence from a preclinical model Bronzuoli, Maria Rosanna Facchinetti, Roberta Ingrassia, Davide Sarvadio, Michela Schiavi, Sara Steardo, Luca Verkhratsky, Alexei Trezza, Viviana Scuderi, Caterina Mol Autism Research BACKGROUND: Neuroglial cells that provide homeostatic support and form defence of the nervous system contribute to all neurological disorders. We analyzed three major types of neuroglia, astrocytes, oligodendrocytes, and microglia in the brains of an animal model of autism spectrum disorder, in which rats were exposed prenatally to antiepileptic and mood stabilizer drug valproic acid; this model being of acknowledged clinical relevance. METHODS: We tested the autistic-like behaviors of valproic acid-prenatally exposed male rats by performing isolation-induced ultrasonic vocalizations, the three-chamber test, and the hole board test. To account for human infancy, adolescence, and adulthood, such tasks were performed at postnatal day 13, postnatal day 35, and postnatal day 90, respectively. After sacrifice, we examined gene and protein expression of specific markers of neuroglia in hippocampus, prefrontal cortex, and cerebellum, these brain regions being associated with autism spectrum disorder pathogenesis. RESULTS: Infant offspring of VPA-exposed dams emitted less ultrasonic vocalizations when isolated from their mothers and siblings and, in adolescence and adulthood, they showed altered sociability in the three chamber test and increased stereotypic behavior in the hole board test. Molecular analyses indicate that prenatal valproic acid exposure affects all types of neuroglia, mainly causing transcriptional modifications. The most prominent changes occur in prefrontal cortex and in the hippocampus of autistic-like animals; these changes are particularly evident during infancy and adolescence, while they appear to be mitigated in adulthood. CONCLUSIONS: Neuroglial pathological phenotype in autism spectrum disorder rat model appears to be rather mild with little signs of widespread and chronic neuroinflammation. BioMed Central 2018-12-27 /pmc/articles/PMC6307226/ /pubmed/30603062 http://dx.doi.org/10.1186/s13229-018-0254-0 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bronzuoli, Maria Rosanna
Facchinetti, Roberta
Ingrassia, Davide
Sarvadio, Michela
Schiavi, Sara
Steardo, Luca
Verkhratsky, Alexei
Trezza, Viviana
Scuderi, Caterina
Neuroglia in the autistic brain: evidence from a preclinical model
title Neuroglia in the autistic brain: evidence from a preclinical model
title_full Neuroglia in the autistic brain: evidence from a preclinical model
title_fullStr Neuroglia in the autistic brain: evidence from a preclinical model
title_full_unstemmed Neuroglia in the autistic brain: evidence from a preclinical model
title_short Neuroglia in the autistic brain: evidence from a preclinical model
title_sort neuroglia in the autistic brain: evidence from a preclinical model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307226/
https://www.ncbi.nlm.nih.gov/pubmed/30603062
http://dx.doi.org/10.1186/s13229-018-0254-0
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