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, L., Depino, A.M.
Formato: INPR
Lenguaje:English
Materias:
Astroglia
Behavior
Cytokines
Hypothalamus-pituitary-adrenal axis
Microglia
Valproic acid
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19393792_v_n_p_Lucchina
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id todo:paper_19393792_v_n_p_Lucchina
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spelling todo:paper_19393792_v_n_p_Lucchina2023-10-03T16:36:51Z Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism Lucchina, L. Depino, A.M. Astroglia Behavior Cytokines Hypothalamus-pituitary-adrenal axis Microglia 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. © 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. INPR English info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19393792_v_n_p_Lucchina
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language English
orig_language_str_mv English
topic Astroglia
Behavior
Cytokines
Hypothalamus-pituitary-adrenal axis
Microglia
Valproic acid
spellingShingle Astroglia
Behavior
Cytokines
Hypothalamus-pituitary-adrenal axis
Microglia
Valproic acid
Lucchina, L.
Depino, A.M.
Altered Peripheral and Central Inflammatory Responses in a Mouse Model of Autism
topic_facet Astroglia
Behavior
Cytokines
Hypothalamus-pituitary-adrenal axis
Microglia
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. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
format INPR
author Lucchina, L.
Depino, A.M.
author_facet Lucchina, L.
Depino, A.M.
author_sort Lucchina, L.
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
url http://hdl.handle.net/20.500.12110/paper_19393792_v_n_p_Lucchina
work_keys_str_mv AT lucchinal alteredperipheralandcentralinflammatoryresponsesinamousemodelofautism
AT depinoam alteredperipheralandcentralinflammatoryresponsesinamousemodelofautism
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