PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
Impact of Maternal Immune Activation Early in Pregnancy on Brain Development of Offspring: A Combined Morphological, Spectroscopic, and Behavioral Study
Version 1
: Received: 3 March 2022 / Approved: 10 March 2022 / Online: 10 March 2022 (03:06:59 CET)
How to cite:
Cupo, L.; Guma, E.; Gallino, D.; Mar, K.; Fowler, C.; Dehghani, M.; Near, J.; Devenyi, G.; Chakravarty, M. Impact of Maternal Immune Activation Early in Pregnancy on Brain Development of Offspring: A Combined Morphological, Spectroscopic, and Behavioral Study. Preprints2022, 2022030136. https://doi.org/10.20944/preprints202203.0136.v1
Cupo, L.; Guma, E.; Gallino, D.; Mar, K.; Fowler, C.; Dehghani, M.; Near, J.; Devenyi, G.; Chakravarty, M. Impact of Maternal Immune Activation Early in Pregnancy on Brain Development of Offspring: A Combined Morphological, Spectroscopic, and Behavioral Study. Preprints 2022, 2022030136. https://doi.org/10.20944/preprints202203.0136.v1
Cupo, L.; Guma, E.; Gallino, D.; Mar, K.; Fowler, C.; Dehghani, M.; Near, J.; Devenyi, G.; Chakravarty, M. Impact of Maternal Immune Activation Early in Pregnancy on Brain Development of Offspring: A Combined Morphological, Spectroscopic, and Behavioral Study. Preprints2022, 2022030136. https://doi.org/10.20944/preprints202203.0136.v1
APA Style
Cupo, L., Guma, E., Gallino, D., Mar, K., Fowler, C., Dehghani, M., Near, J., Devenyi, G., & Chakravarty, M. (2022). Impact of Maternal Immune Activation Early in Pregnancy on Brain Development of Offspring: A Combined Morphological, Spectroscopic, and Behavioral Study. Preprints. https://doi.org/10.20944/preprints202203.0136.v1
Chicago/Turabian Style
Cupo, L., Gabriel Devenyi and Mallar Chakravarty. 2022 "Impact of Maternal Immune Activation Early in Pregnancy on Brain Development of Offspring: A Combined Morphological, Spectroscopic, and Behavioral Study" Preprints. https://doi.org/10.20944/preprints202203.0136.v1
Abstract
Serological human birth cohort studies have identified maternal infection during pregnancy as a risk factor for development of disorders such as Autism Spectrum Disorder and schizophrenia in offspring. Similarly, in experiments using animal models, maternal immune activation (MIA) has been shown to alter neuroanatomical and behavioral development in offspring. This study employs magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in conjunction with behavioral assays to refine our understanding of the impact of MIA on neurobiological development in exposed animals. On gestational day nine, pregnant dams were injected with either polyinosinic:polycytidylic acid (POL) to induce MIA or saline (SAL) as a control. Whole-brain MRI, localized proton MRS, and behavioral tests (open field, three chambered social approach, and prepulse inhibition) were acquired at two timepoints, during adolescence (postnatal day [PND] 35) and adulthood (PND 60). Whole-brain voxel-wise volumetric analyses revealed that MIA offspring exhibited altered volume in the hippocampus and caudate putamen (CPu) between adolescence and early adulthood. MRS data were assessed at each timepoint separately; MIA offspring during early adulthood but not adolescence exhibited trending reductions in γ-aminobutyrate (GABA) (p = 0.06) and myo-inositol (Ins) (p = 0.08) compared to saline controls. However, these metabolite differences did not reach levels of significance, even before multiple comparison corrections. Open field testing revealed that during adolescence, MIA offspring displayed a more anxious phenotype than controls wherein they spent less time in the anxiogenic center zone of the open field arena (p < 0.007), but this difference normalized by adulthood. There were no significant differences in sociability preference, novelty preference, or prepulse inhibition comparing the groups. Results suggest that early gestational exposure to MIA results in subtle neuroanatomical changes in the trajectories of development, trending behavioral changes in adolescent offspring, and slight neurochemical changes in young adult offspring. Maternal infection alone may not be enough; additional genetic or environmental risk factors may be required to elicit the more typical symptoms of neuropsychiatric disorders.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received:
8 January 2023
Commenter:
Richard Maddock
The commenter has declared there is no conflict of interests.
Comment:
Excellent study and report. I was a little surprised to see in the discussion of inositol findings in schizophrenia that only reports of elevated inositol were mentioned. Das et al. reported the results of a meta-analysis in 2018 and found a small but significant reduction in medial prefrontal cortex inositol across 19 studies of patients with schizophrenia. It seems like the trend toward reduced inositol in your mouse MIA model is consistent with that meta-analytic finding. Or perhaps you view the Das meta-analysis as flawed in some way...
In any case, I look forward to seeing the final publication.
Commenter: Richard Maddock
The commenter has declared there is no conflict of interests.
In any case, I look forward to seeing the final publication.