Aperçu: G.M.
Les
défis de la petite enfance, en particulier les infections et le stress,
sont liés à des troubles neuropsychiatriques tels que l'autisme et la
schizophrénie. Ici,
les auteurs ont mené un large éventail de tests comportementaux chez les
souris périadolescentes (postnatal day (PN) 35) et adultes (PN70)
néonatales avec LPS sur PN5 et -7, pour dévoiler des altérations
comportementales déclenchées par l'exposition au LPS.
Les
modifications de l'immunité innée et de la parvalbumine ont été les
principales remarques induites par le LPS chez les mâles et les femelles de l'étude.
Les chercheurs ont conclu que le problème LPS néonatal déclenche des altérations
comportementales et neurochimiques spécifiques au sexe qui ressemblent
au "trouble du spectre de l'autisme", ce qui constitue un modèle pertinent
pour l'étude mécaniste du biais sexuel associé au développement de ce
trouble.
Mol Neurobiol. 2017 May 23. doi: 10.1007/s12035-017-0616-1.
Neonatal Immune Challenge with Lipopolysaccharide Triggers Long-lasting Sex- and Age-related Behavioral and Immune/Neurotrophic Alterations in Mice: Relevance to Autism Spectrum Disorders
Custódio CS1,2, Mello BSF1,2, Filho AJMC1, de Carvalho Lima CN1, Cordeiro RC1,2, Miyajima F1,3, Réus GZ4, Vasconcelos SMM1, Barichello T5,6,7, Quevedo J5,6,7, de Oliveira AC8, de Lucena DF1, Macedo DS9,10,11.
Author information
- 1
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60430-270, Brazil.
- 2
- Medical Microbiology Postgraduate Program, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, CE, Brazil.
- 3
- University of Liverpool Institute of Translational Medicine, Wolfson Centre, Block A: Waterhouse Building, 1-5 Brownlow Street, Liverpool, L69 3GL, UK.
- 4
- Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
- 5
- Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
- 6
- Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA.
- 7
- Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
- 8
- Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
- 9
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Universidade Federal do Ceará, Rua Cel. Nunes de Melo 1000, Fortaleza, CE, 60430-270, Brazil. daniellesilmacedo@gmail.com
- 10
- Medical Microbiology Postgraduate Program, Faculty of Medicine, Universidade Federal do Ceará, Fortaleza, CE, Brazil. daniellesilmacedo@gmail.com.
- 11
- National Science and Technology Institute for Translational Medicine (INCT-TM), Houston, Brazil. daniellesilmacedo@gmail.com.
Abstract
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.
- PMID: 28536974
- DOI: 10.1007/s12035-017-0616-1
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