Mapping the impact of exposure to maternal immune activation on juvenile Wistar rat brain macro- and microstructure
Tobias C Wood1, Michelle E Edye2, Michael K Harte2
1Centre for Neuroimaging Sciences, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Insights
Maternal immune activation in pregnant rats, induced by polyriboinosinic-polyribocytidylic acid, led to subtle neuroanatomical changes in offspring. Specifically, the diagonal domain volume increased, suggesting potential long-term brain development impacts.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Maternal immune activation is linked to increased psychiatric disorder risk in offspring.
- Previous studies assessed immediate effects of polyriboinosinic-polyribocytidylic acid exposure on physiological and neuropathological markers.
Purpose of the Study:
- To investigate the mesoscale neuroanatomical impact of gestational maternal immune activation on juvenile rat brains.
- To complement and extend previous findings on the effects of polyriboinosinic-polyribocytidylic acid exposure during gestation.
Main Methods:
- High-resolution, ex vivo anatomical magnetic resonance imaging (MRI) was used to assess brain structure.
- Atlas-based segmentation was employed for detailed neuroanatomical analysis.
- Diffusion tensor imaging (DTI) was utilized to detect microstructural alterations.
Main Results:
- A statistically significant increase in the relative volume of the diagonal domain was observed in offspring exposed to polyriboinosinic-polyribocytidylic acid during gestation (p < 0.01 uncorrected).
- This finding narrowly missed stringent multiple comparisons correction (q = 0.07).
- No significant microstructural changes were detected using diffusion tensor imaging.
Conclusions:
- Gestational maternal immune activation may induce subtle, specific neuroanatomical alterations in the developing rat brain.
- Further research is needed to confirm these findings and map the effects across development.
- The study highlights the potential long-term consequences of maternal immune activation on offspring neurodevelopment.
Abstract:
Maternal immune activation is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of maternal immune activation effects across the lifespan. In this context, we recently reported the effects of polyriboinosinic-polyribocytidylic acid-induced maternal immune activation at gestational day 15, immediately prior to birth, at gestational day 21 and again at post-natal day 21, providing a systematic assessment of plasma interleukin 6, body temperature and weight alterations in pregnant rats and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offsprings at these time points. Here, we sought to complement and extend these data by characterising in more detail the mesoscale impact of gestational polyriboinosinic-polyribocytidylic acid exposure at gestational day 15 on the neuroanatomy of the juvenile (post-natal day 21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational polyriboinosinic-polyribocytidylic acid exposure (n = 10) relative to saline controls (n = 10) at this time-point. Specifically, we found an increase in the relative volume of the diagonal domain in polyriboinosinic-polyribocytidylic acid offspring (p < 0.01 uncorrected), which just failed to pass stringent multiple comparisons correction (actual q = 0.07). No statistically significant microstructural alterations were detectable using diffusion tensor imaging. Further studies are required to map the proximal effects of maternal immune activation on the developing rodent brain from foetal to early post-natal life and confirm our findings herein.
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