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Long-term effects of preterm birth on behavior and neurosteroid sensitivity in the guinea pig
Julia C Shaw1,2, Hannah K Palliser1,2, Rebecca M Dyson3
1School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Insights
Juvenile ex-preterm male guinea pigs show hyperactivity and impaired neurodevelopment, including lower myelination and altered GABAA receptor levels. This establishes a valuable model for studying neurodevelopmental disorders in ex-preterm individuals.
Area of Science:
- Neuroscience
- Developmental Biology
- Animal Models
Background:
- Ex-preterm children face risks for late-onset neurodevelopmental and behavioral disorders.
- Mechanisms underlying these disorders are not fully understood.
- There is a need for relevant animal models to study these conditions.
Purpose of the Study:
- To establish and characterize a guinea pig model of ex-preterm neurodevelopment.
- To investigate behavioral and neurobiological differences between ex-preterm and term-born juvenile males.
- To assess the suitability of this model for future therapeutic research.
Main Methods:
- Ex-preterm and term-born guinea pigs were behaviorally tested and tissues collected.
- Neurodevelopmental markers (myelin basic protein, glial fibrillary acidic protein) were analyzed via immunohistochemistry.
- Gamma-aminobutyric acid A receptor subunit mRNA and salivary cortisol levels were quantified.
Main Results:
- Ex-preterm males exhibited hyperactivity, increased exploration, and social interaction.
- Lower myelination and reactive astrocyte coverage were observed in the ex-preterm male brain.
- Reduced hippocampal α5 subunit mRNA and elevated baseline salivary cortisol were found in ex-preterm males.
Conclusions:
- Juvenile ex-preterm male guinea pigs display a hyperactive phenotype and impaired neurodevelopment.
- This model demonstrates key features relevant to neurodevelopmental disorders in ex-preterm individuals.
- The established guinea pig model is suitable for future therapeutic intervention studies.
Background:
Ex-preterm children and adolescents are at risk of developing late-onset neurodevelopmental and behavioral disorders. The mechanisms by which this happens are poorly understood and relevant animal models are required.
Methods:
Ex-preterm (delivered at 62 d gestation) and term (spontaneously delivered) juvenile guinea pigs underwent behavioral testing at 25 d corrected postnatal age, with tissues collected at 28 d. Neurodevelopmental markers (myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP)) were analyzed in the hippocampus and subcortical white matter by immunohistochemistry. Gamma-aminobutyric acid A (GABAA) receptor subunit mRNA levels were quantified by reverse transcription polymerase chain reaction (RT-PCR), and salivary cortisol measured by enzyme-linked immunosorbent assay.
Results:
Preterm males travelled greater distances, were mobile for longer, spent more time investigating objects, and approached or interacted with familiar animals more than controls. Myelination and reactive astrocyte coverage was lower in the hippocampus and the subcortical white matter in preterm males. Hippocampal levels of the α5 subunit were also lower in the preterm male brain. Baseline salivary cortisol was higher for preterm males compared to controls.
Conclusion:
We conclude that juvenile ex-preterm male guinea pigs exhibit a hyperactive phenotype and feature impaired neurodevelopment, making this a suitable model for future therapeutic studies.
