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Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology

Neurodevelopmental disorders stemming from maternal immune activation can significantly affect a child’s life. A major limitation in pre-clinical studies is the scarcity of valid animal models that accurately mimic these challenges. Among the available models, administration of lipopolysaccharide (L...

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Autores principales: Pavlov, Dmitrii, Gorlova, Anna, Haque, Abrar, Cavalcante, Carlos, Svirin, Evgeniy, Burova, Alisa, Grigorieva, Elizaveta, Sheveleva, Elizaveta, Malin, Dmitry, Efimochkina, Sofia, Proshin, Andrey, Umriukhin, Aleksei, Morozov, Sergey, Strekalova, Tatyana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380915/
https://www.ncbi.nlm.nih.gov/pubmed/37511470
http://dx.doi.org/10.3390/ijms241411712
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author Pavlov, Dmitrii
Gorlova, Anna
Haque, Abrar
Cavalcante, Carlos
Svirin, Evgeniy
Burova, Alisa
Grigorieva, Elizaveta
Sheveleva, Elizaveta
Malin, Dmitry
Efimochkina, Sofia
Proshin, Andrey
Umriukhin, Aleksei
Morozov, Sergey
Strekalova, Tatyana
author_facet Pavlov, Dmitrii
Gorlova, Anna
Haque, Abrar
Cavalcante, Carlos
Svirin, Evgeniy
Burova, Alisa
Grigorieva, Elizaveta
Sheveleva, Elizaveta
Malin, Dmitry
Efimochkina, Sofia
Proshin, Andrey
Umriukhin, Aleksei
Morozov, Sergey
Strekalova, Tatyana
author_sort Pavlov, Dmitrii
collection PubMed
description Neurodevelopmental disorders stemming from maternal immune activation can significantly affect a child’s life. A major limitation in pre-clinical studies is the scarcity of valid animal models that accurately mimic these challenges. Among the available models, administration of lipopolysaccharide (LPS) to pregnant females is a widely used paradigm. Previous studies have reported that a model of ‘emotional stress’, involving chronic exposure of rodents to ultrasonic frequencies, induces neuroinflammation, aberrant neuroplasticity, and behavioral deficits. In this study, we explored whether this model is a suitable paradigm for maternal stress and promotes neurodevelopmental abnormalities in the offspring of stressed females. Pregnant dams were exposed to ultrasound stress for 21 days. A separate group was injected with LPS on embryonic days E11.5 and E12.5 to mimic prenatal infection. The behavior of the dams and their female offspring was assessed using the sucrose test, open field test, and elevated plus maze. Additionally, the three-chamber sociability test and Barnes maze were used in the offspring groups. ELISA and qPCR were used to examine pro-inflammatory changes in the blood and hippocampus of adult females. Ultrasound-exposed adult females developed a depressive-like syndrome, hippocampal overexpression of GSK-3β, IL-1β, and IL-6 and increased serum concentrations of IL-1β, IL-6, IL-17, RANTES, and TNFα. The female offspring also displayed depressive-like behavior, as well as cognitive deficits. These abnormalities were comparable to the behavioral changes induced by LPS. The ultrasound stress model can be a promising animal paradigm of neurodevelopmental pathology associated with prenatal ‘emotional stress’.
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spelling pubmed-103809152023-07-29 Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology Pavlov, Dmitrii Gorlova, Anna Haque, Abrar Cavalcante, Carlos Svirin, Evgeniy Burova, Alisa Grigorieva, Elizaveta Sheveleva, Elizaveta Malin, Dmitry Efimochkina, Sofia Proshin, Andrey Umriukhin, Aleksei Morozov, Sergey Strekalova, Tatyana Int J Mol Sci Article Neurodevelopmental disorders stemming from maternal immune activation can significantly affect a child’s life. A major limitation in pre-clinical studies is the scarcity of valid animal models that accurately mimic these challenges. Among the available models, administration of lipopolysaccharide (LPS) to pregnant females is a widely used paradigm. Previous studies have reported that a model of ‘emotional stress’, involving chronic exposure of rodents to ultrasonic frequencies, induces neuroinflammation, aberrant neuroplasticity, and behavioral deficits. In this study, we explored whether this model is a suitable paradigm for maternal stress and promotes neurodevelopmental abnormalities in the offspring of stressed females. Pregnant dams were exposed to ultrasound stress for 21 days. A separate group was injected with LPS on embryonic days E11.5 and E12.5 to mimic prenatal infection. The behavior of the dams and their female offspring was assessed using the sucrose test, open field test, and elevated plus maze. Additionally, the three-chamber sociability test and Barnes maze were used in the offspring groups. ELISA and qPCR were used to examine pro-inflammatory changes in the blood and hippocampus of adult females. Ultrasound-exposed adult females developed a depressive-like syndrome, hippocampal overexpression of GSK-3β, IL-1β, and IL-6 and increased serum concentrations of IL-1β, IL-6, IL-17, RANTES, and TNFα. The female offspring also displayed depressive-like behavior, as well as cognitive deficits. These abnormalities were comparable to the behavioral changes induced by LPS. The ultrasound stress model can be a promising animal paradigm of neurodevelopmental pathology associated with prenatal ‘emotional stress’. MDPI 2023-07-20 /pmc/articles/PMC10380915/ /pubmed/37511470 http://dx.doi.org/10.3390/ijms241411712 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pavlov, Dmitrii
Gorlova, Anna
Haque, Abrar
Cavalcante, Carlos
Svirin, Evgeniy
Burova, Alisa
Grigorieva, Elizaveta
Sheveleva, Elizaveta
Malin, Dmitry
Efimochkina, Sofia
Proshin, Andrey
Umriukhin, Aleksei
Morozov, Sergey
Strekalova, Tatyana
Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology
title Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology
title_full Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology
title_fullStr Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology
title_full_unstemmed Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology
title_short Maternal Chronic Ultrasound Stress Provokes Immune Activation and Behavioral Deficits in the Offspring: A Mouse Model of Neurodevelopmental Pathology
title_sort maternal chronic ultrasound stress provokes immune activation and behavioral deficits in the offspring: a mouse model of neurodevelopmental pathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10380915/
https://www.ncbi.nlm.nih.gov/pubmed/37511470
http://dx.doi.org/10.3390/ijms241411712
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