Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism

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Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneous...

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Autores principales:	Lucchina, Luciana, Depino, Amaicha Mara
Publicado:	2014
Materias:	Astroglia Behavior Cytokines Hypothalamus-pituitary-adrenal axis Microglia Valproic acid corticosterone cytokine lipopolysaccharide valproic acid autacoid adult animal experiment animal model animal tissue article autism cerebellum controlled study corticosterone release elevated plus maze test female glia hippocampus male microglial cell culture mouse nervous system inflammation nonhuman pathogenesis priority journal social interaction spleen animal biological model blood chemically induced immunology pregnancy prenatal exposure real time polymerase chain reaction Animals Cerebellum Child Development Disorders, Pervasive Corticosterone Female Hippocampus Inflammation Mediators Lipopolysaccharides Mice Models, Genetic Neuroglia Pregnancy Prenatal Exposure Delayed Effects Real-Time Polymerase Chain Reaction Valproic Acid
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19393792_v7_n2_p273_Lucchina http://hdl.handle.net/20.500.12110/paper_19393792_v7_n2_p273_Lucchina
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_19393792_v7_n2_p273_Lucchina
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spelling	paper:paper_19393792_v7_n2_p273_Lucchina2023-06-08T16:32:16Z Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism Lucchina, Luciana Depino, Amaicha Mara Astroglia Behavior Cytokines Hypothalamus-pituitary-adrenal axis Microglia Valproic acid corticosterone cytokine lipopolysaccharide valproic acid autacoid corticosterone cytokine valproic acid adult animal experiment animal model animal tissue article autism cerebellum controlled study corticosterone release elevated plus maze test female glia hippocampus male microglial cell culture mouse nervous system inflammation nonhuman pathogenesis priority journal social interaction spleen animal autism biological model blood chemically induced immunology pregnancy prenatal exposure real time polymerase chain reaction Animals Cerebellum Child Development Disorders, Pervasive Corticosterone Cytokines Female Hippocampus Inflammation Mediators Lipopolysaccharides Mice Models, Genetic Neuroglia Pregnancy Prenatal Exposure Delayed Effects Real-Time Polymerase Chain Reaction Valproic Acid Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism-related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. Autism Res 2013, 7: 273-289. © 2013 International Society for Autism Research, Wiley Periodicals, Inc. Fil:Lucchina, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Depino, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19393792_v7_n2_p273_Lucchina http://hdl.handle.net/20.500.12110/paper_19393792_v7_n2_p273_Lucchina
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Astroglia Behavior Cytokines Hypothalamus-pituitary-adrenal axis Microglia Valproic acid corticosterone cytokine lipopolysaccharide valproic acid autacoid corticosterone cytokine valproic acid adult animal experiment animal model animal tissue article autism cerebellum controlled study corticosterone release elevated plus maze test female glia hippocampus male microglial cell culture mouse nervous system inflammation nonhuman pathogenesis priority journal social interaction spleen animal autism biological model blood chemically induced immunology pregnancy prenatal exposure real time polymerase chain reaction Animals Cerebellum Child Development Disorders, Pervasive Corticosterone Cytokines Female Hippocampus Inflammation Mediators Lipopolysaccharides Mice Models, Genetic Neuroglia Pregnancy Prenatal Exposure Delayed Effects Real-Time Polymerase Chain Reaction Valproic Acid
spellingShingle	Astroglia Behavior Cytokines Hypothalamus-pituitary-adrenal axis Microglia Valproic acid corticosterone cytokine lipopolysaccharide valproic acid autacoid corticosterone cytokine valproic acid adult animal experiment animal model animal tissue article autism cerebellum controlled study corticosterone release elevated plus maze test female glia hippocampus male microglial cell culture mouse nervous system inflammation nonhuman pathogenesis priority journal social interaction spleen animal autism biological model blood chemically induced immunology pregnancy prenatal exposure real time polymerase chain reaction Animals Cerebellum Child Development Disorders, Pervasive Corticosterone Cytokines Female Hippocampus Inflammation Mediators Lipopolysaccharides Mice Models, Genetic Neuroglia Pregnancy Prenatal Exposure Delayed Effects Real-Time Polymerase Chain Reaction Valproic Acid Lucchina, Luciana Depino, Amaicha Mara Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
topic_facet	Astroglia Behavior Cytokines Hypothalamus-pituitary-adrenal axis Microglia Valproic acid corticosterone cytokine lipopolysaccharide valproic acid autacoid corticosterone cytokine valproic acid adult animal experiment animal model animal tissue article autism cerebellum controlled study corticosterone release elevated plus maze test female glia hippocampus male microglial cell culture mouse nervous system inflammation nonhuman pathogenesis priority journal social interaction spleen animal autism biological model blood chemically induced immunology pregnancy prenatal exposure real time polymerase chain reaction Animals Cerebellum Child Development Disorders, Pervasive Corticosterone Cytokines Female Hippocampus Inflammation Mediators Lipopolysaccharides Mice Models, Genetic Neuroglia Pregnancy Prenatal Exposure Delayed Effects Real-Time Polymerase Chain Reaction Valproic Acid
description	Increasing clinical and experimental evidence links immune and inflammatory alterations with the pathogenesis of autism spectrum disorders (ASD). Autistic individuals show signs of neuroinflammation, altered inflammatory responses, and immune abnormalities throughout life. Mice injected subcutaneously with 600mg/kg valproic acid (VPA600) at gestational day 12.5 show reduced social interaction in adulthood (at 8 weeks of age), and they have been proposed as a mouse model of autism. Here, we show that these adult animals present signs of chronic glial activation in the hippocampus and the cerebellum. Moreover, when they are challenged with a peripheral inflammatory stimulus (intraperitoneal lipopolysaccharides, LPS), VPA600 animals show an exacerbated inflammatory response. Two hours after LPS injection, VPA600 animals secrete more corticosterone to the blood than control mice, and show an increase in the levels of expression of proinflammatory cytokines in the spleen. After LPS challenge, VPA600 mice also show signs of increased neuroinflammation compared with control mice: they have more microglial cells in the hippocampus, and they show higher levels of proinflammatory cytokines in the cerebellum. Our results provide evidence of basal neuroinflammation and an altered inflammatory response in the VPA model of autism. We propose that this model can be used to evaluate the contribution of inflammatory reactivity to autism-related behaviors. These studies will contribute to elucidate the role of the inflammatory alterations observed in ASD individuals. Autism Res 2013, 7: 273-289. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
author	Lucchina, Luciana Depino, Amaicha Mara
author_facet	Lucchina, Luciana Depino, Amaicha Mara
author_sort	Lucchina, Luciana
title	Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
title_short	Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
title_full	Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
title_fullStr	Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
title_full_unstemmed	Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
title_sort	altered peripheral and central inflammatory responses in a mouse model of autism
publishDate	2014
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19393792_v7_n2_p273_Lucchina http://hdl.handle.net/20.500.12110/paper_19393792_v7_n2_p273_Lucchina
work_keys_str_mv	AT lucchinaluciana alteredperipheralandcentralinflammatoryresponsesinamousemodelofautism AT depinoamaichamara alteredperipheralandcentralinflammatoryresponsesinamousemodelofautism
_version_	1768546559292604416

Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism

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