Neonatal Immune Challenge with Lipopolysaccharide Triggers Long-lasting Sex- and Age-related Behavioral and Immune/Neurotrophic Alterations in Mice: Relevance to Autism Spectrum Disorders
| Autor: | David Freitas de Lucena, Danielle Silveira Macêdo, Camila Nayane de Carvalho Lima, Fabio Miyajima, Bruna Stefânia Ferreira Mello, João Quevedo, Adriano José Maia Chaves Filho, Rafaela Carneiro Cordeiro, Silvânia Maria Mendes Vasconcelos, Antonio C. de Oliveira, Gislaine Z. Réus, Tatiana Barichello, Charllyany Sabino Custódio |
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| Rok vydání: | 2017 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine medicine.medical_specialty Autism Spectrum Disorder Hypothalamus Neuroscience (miscellaneous) Prefrontal Cortex Hippocampus Mice 03 medical and health sciences Cellular and Molecular Neuroscience Sex Factors 0302 clinical medicine Neurochemical Internal medicine medicine Animals Maze Learning Prefrontal cortex Prepulse inhibition Brain-derived neurotrophic factor Behavior Animal Brain-Derived Neurotrophic Factor Age Factors medicine.disease Disease Models Animal Memory Short-Term 030104 developmental biology Endocrinology Neurology Autism spectrum disorder Schizophrenia Immunology Autism Female Lipid Peroxidation Psychology 030217 neurology & neurosurgery |
| Zdroj: | Molecular Neurobiology. |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | Early-life challenges, particularly infections and stress, are related to neuropsychiatric disorders such as autism and schizophrenia. Here, we conducted a wide range of behavioral tests in periadolescent (postnatal day (PN) 35) and adult (PN70) Swiss mice neonatally challenged with LPS on PN5 and -7, to unveil behavioral alterations triggered by LPS exposure. Immune and neurotrophic (brain-derived neurotrophic factor-BDNF) alterations were determined in the prefrontal cortex (PFC), hippocampus (HC), and hypothalamus (HT). Since the incidence and clinical manifestations of neurodevelopmental disorders present significant sex-related differences, we sought to distinctly evaluate male and female mice. While on PN35, LPS-challenged male mice presented depressive, anxiety-like, repetitive behavior, and working memory deficits; on PN70, only depressive- and anxiety-like behaviors were observed. Conversely, females presented prepulse inhibition (PPI) deficits in both ages studied. Behavioral changes in periadolescence and adulthood were accompanied, in both sexes, by increased levels of interleukin (IL-4) (PFC, HC, and HT) and decreased levels of IL-6 (PFC, HC, and HT). BDNF levels increased in both sexes on PN70. LPS-challenged male mice presented, in both ages evaluated, increased HC myeloperoxidase activity (MPO); while when adult increased levels of interferon gamma (IFNγ), nitrite and decreased parvalbumin were observed. Alterations in innate immunity and parvalbumin were the main LPS-induced remarks between males and females in our study. We concluded that neonatal LPS challenge triggers sex-specific behavioral and neurochemical alterations that resemble autism spectrum disorder, constituting in a relevant model for the mechanistic investigation of sex bias associated with the development of this disorder. |
| Databáze: | OpenAIRE |
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