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Updated: Oct 18, 2025
A Gut-on-a-Chip Model to Study the Gut Microbiome-Nervous System Axis
Published on: July 28, 2023
Investigating the gut-brain axis in a neurodevelopmental rodent model of schizophrenia
Max W Katz-Barber1,2,3,4, Sharon L Hollins1,2,3, Annalisa Cuskelly1,2,3
1Laboratory of Neuroimmunology, School of Psychology, University of Newcastle, Callaghan, NSW, Australia.
Background:
Although the aetiology of schizophrenia remains unknown, it has been suggested that it might occur in response to alterations in the gut-brain axis (GBA), the bi-directional communication system between the gut and the brain. The current study aimed to determine whether the "two-hit" animal model of neuropsychopathology (maternal immune activation combined with adolescent cannabinoid exposure), produced abnormalities in the GBA.
Method:
Pregnant Wistar rats were administered the viral mimetic polyI:C on gestational day 19 and offspring were administered the synthetic cannabinoid HU210 from postnatal days 35-48. Evidence of GBA activation was assessed in the hypothalamus, colon and fecal samples from male and female offspring at adolescence and adulthood.
Results:
Findings were sex-specific with adolescent female offspring exhibiting an increased hypothalamic inflammatory profile, increased hypothalamic CRHR1 mRNA, and decreased fecal expression of Bifidobacterium longum, however, no changes were detected in colonic inflammation or integrity.
Conclusion:
These results indicate that the rat two-hit model, documented to produce behavioural and neuroanatomical abnormalities, also produces hypothalamic and microbiota abnormalities. The results also demonstrate significant sex differences, suggesting that this model may be useful for investigating the role of the GBA in the aetiology of neurodevelopmental disorders such as schizophrenia.
