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Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)
Published on: April 23, 2015
Aberrant immune responses in a mouse with behavioral disorders.
Yong Heo1, Yubin Zhang, Donghong Gao
1College of Natural Sciences, Catholic University of Daegu, Kyongsan-si, Republic of Korea.
Plos One
|July 30, 2011
Summary
BTBR mice, exhibiting autistic-like behaviors, show heightened immune activity, including increased antibodies and brain inflammation. This suggests an autoimmune link to their neurodevelopmental differences.
Area of Science:
- Neuroimmunology
- Behavioral Neuroscience
- Immunology
Background:
- BTBR mice display social interaction deficits and repetitive behaviors, mirroring autism spectrum disorder (ASD) traits.
- Aberrant immune activity is observed in individuals with autism, suggesting a potential link between immunity and neurodevelopment.
- Autoimmune responses are known to influence behavior, prompting an investigation into the immune system of BTBR mice.
Purpose of the Study:
- To evaluate and compare the immune system and neuroinflammation in BTBR mice against C57BL/6 (B6) mice and their F1 offspring.
- To investigate the potential role of autoimmune processes in the aberrant behaviors observed in BTBR mice.
Main Methods:
- Assessment of serum immunoglobulin G (IgG) and immunoglobulin E (IgE) levels, anti-brain antibodies, and brain-deposited IgG and IgE.
- Measurement of cytokine expression (IL-33, IL-18, IL-1β) and microglial activation (MHC class II) in the brain.
- Evaluation of B cell populations (CD40(hi)/I-A(hi), IgG-secreting B cells) and antibody production following keyhole limpet hemocyanin (KLH) immunization.
- Assessment of susceptibility to listeriosis.
Main Results:
- BTBR mice exhibited significantly higher serum IgG and IgE, IgG anti-brain antibodies, and brain deposition of IgG and IgE compared to B6 mice.
- Elevated expression of IL-33, IL-18, and IL-1β, along with increased MHC class II-expressing microglia, was observed in BTBR mice brains.
- BTBR mice showed increased CD40(hi)/I-A(hi) B cells and IgG-secreting B cells, producing more anti-KLH antibodies upon immunization.
- F1 offspring displayed intermediate levels of antibodies and cytokines, correlating with social activity.
- BTBR mice were more susceptible to listeriosis than B6 or BALB/c mice, indicating impaired cellular immunity.
Conclusions:
- The Th2-biased immune profile and constitutive neuroinflammation in BTBR mice support an autoimmune etiology for their behavioral abnormalities.
- Findings suggest that autoimmune mechanisms may contribute to autism-like behaviors, offering a potential parallel with observed immune dysregulation in humans with autism.
