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Strategies for Assessing Autistic-Like Behaviors in Mice

Strategies for Assessing Autistic-Like Behaviors in Mice

Published on: September 20, 2024

Interleukin-18 modulation in autism spectrum disorders.

Rita Businaro¹, Mariangela Corsi², Gabriella Azzara³

¹Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100, Latina, Italy. rita.businaro@uniroma1.it.

Journal of Neuroinflammation

|January 6, 2016

Summary

Interleukin-18 (IL-18) levels are dysregulated in autism spectrum disorder (ASD), showing decreased serum levels in patients and increased brain levels in a mouse model. Further research is needed to explore IL-18 as a potential ASD biomarker.

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Dynamic Clamp Methods to Investigate Impaired Neuronal Excitability Associated with Autism

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Area of Science:

Neuroscience
Immunology
Genetics

Background:

Autism spectrum disorder (ASD) is a neurodevelopmental condition with unknown etiology, though neuroinflammation is implicated.
Pro-inflammatory cytokines, including interleukin-18 (IL-18), are suspected to play a role in ASD pathogenesis.
Previous studies suggest cytokine imbalance in both serum and brain tissue of individuals with ASD.

Purpose of the Study:

To investigate the potential dysregulation of IL-18 in the serum of ASD patients across different severity grades.
To analyze IL-18 levels in postmortem brain samples from patients with tuberous sclerosis and inflammatory diseases, and in a mouse model of autism (Reeler mice).
To quantify IL-18 and its binding protein (IL-18BP) in the serum and brain of Reeler mice.

Main Methods:

Serum IL-18 levels were quantified using enzyme-linked immunosorbent assay (ELISA).
Immunohistochemistry was employed to localize IL-18 in brain sections from patients and mice.
Western blotting was used to determine IL-18 and IL-18BP levels in brain homogenates and plasma.

Main Results:

Serum IL-18 levels were significantly decreased in ASD patients compared to healthy controls and in Reeler mice compared to wild-type controls.
IL-18 was detected in glial cells and neurons in the brains of patients with tuberous sclerosis and encephalitis, with only weak glial staining in controls.
Western blot analysis revealed higher IL-18 and IL-18BP concentrations in the brains of Reeler mice compared to wild-type littermates, while plasma IL-18BP levels showed no significant difference.

Conclusions:

Interleukin-18 (IL-18) exhibits dysregulation in autism spectrum disorder (ASD), with decreased serum levels and increased brain levels observed.
Further research is required to elucidate the molecular mechanisms underlying IL-18 alterations in ASD.
Investigating IL-18 as a potential predictive biomarker for ASD, possibly in conjunction with other markers like BDNF, warrants larger cohort studies.