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Strategies for Assessing Autistic-Like Behaviors in Mice
Published on: September 20, 2024
Neonatal infection with Bordetella pertussis promotes autism-like phenotypes in mice
Eoin O'Neill1,2, Lucy Curham1, Caitlín Ní Chasaide1
1Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland.
Insights
Early-life infection with Bordetella pertussis (whooping cough) in mice caused brain inflammation and neurodevelopmental issues. This led to autism spectrum disorder (ASD)-like behaviors in adulthood, suggesting a potential link between pertussis infection and ASD risk.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Infections during early development are suspected contributors to neurodevelopmental disorders.
- The role of specific pathogens, like Bordetella pertussis, in autism spectrum disorder (ASD) pathogenesis remains under investigation.
Purpose of the Study:
- To investigate the impact of neonatal Bordetella pertussis infection on neurodevelopment and behavior in mice.
- To explore the underlying mechanisms of neuroinflammation and neurodevelopmental defects following pertussis infection.
Main Methods:
- Neonatal mice were infected with Bordetella pertussis via respiratory challenge.
- Central nervous system (CNS) changes, immune cell infiltration, and microglial function were assessed.
- ASD-like behaviors were evaluated in young adult mice post-infection.
Main Results:
- B. pertussis infection led to blood-brain barrier disruption and bacterial dissemination into the brain.
- Neuroinflammation was characterized by infiltration of inflammatory monocytes, neutrophils, and CD4 T cells.
- Activated microglia exhibited impaired phagocytic function, causing defective synaptic pruning and disrupted neural circuits.
- Infected mice displayed ASD-like behavioral abnormalities in adulthood.
Conclusions:
- Neonatal Bordetella pertussis infection induces neuroinflammation and neurodevelopmental defects, resulting in autism-like behaviors in mice.
- These findings suggest that B. pertussis infection in infancy may increase the risk of developing autism-like behaviors.
- Further research is warranted to explore the potential role of B. pertussis in human ASD.
Abstract:
Autism spectrum disorder (ASD) has been linked with infections early in life. Here we demonstrate that the infection of neonatal mice with the respiratory pathogen Bordetella pertussis leads to neuroinflammation, neurodevelopmental defects, and ASD-like behaviors. Following the respiratory challenge of neonatal mice with B. pertussis, multiple atypical CNS findings were observed, including blood-brain barrier disruption, dissemination of live B. pertussis bacteria to the brain with the concomitant infiltration of inflammatory monocytes, neutrophils, and activated IL-17A- and IFN-γ-producing CD4 T cells. Microglia from infected mice were activated, with impaired phagocytic function, resulting in defective synaptic pruning and disrupted neuronal circuit formation. Impaired neurodevelopment in B. pertussis-infected post-natal mice was associated with ASD-like behavioral abnormalities in young adulthood. Our data indicate that infection with virulent B. pertussis during infancy increases the risk of autism-like behavior in young adult mice. A study into the potential role of B. pertussis in human ASD is warranted.
