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Effects of prenatal exposure to inflammation coupled with prepubertal stress on prefrontal white matter structure and related molecules in adult mouse offspring

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Abstract

Maternal immune activation (MIA) by inflammatory agents such as lipopolysaccharide (LPS) and prepubertal stress (PS) may individually and collectively affect the central nervous system (CNS) during adulthood. Here, we intended to assess the effects of MIA, alone or combined with PS, on prefrontal white matter structure and its related molecules in adult mice offspring. Pregnant mice received either an i.p. dose of LPS (50 μg/kg) on gestational day 17 (GD17) or normal saline. Their pups were exposed to stress from postnatal days (PD) 30 to PD38 or no stress during prepubertal development. We randomly chose 56-day-old male offspring (n = 2 offspring per mother) from each group and isolated their prefrontal areas according to relevant protocols. The tissue samples were prepared for structural, histological, and molecular examinations. The LPS + stress group had evidence of increased damage in the white matter structures compared to the control, stress, and LPS groups (p < 0.05). The LPS + stress group also had significant downregulation of the genes involved in white matter formation (Sox10, Olig1, myelin regulatory factor, and Wnt compared with the control, stress, and LPS groups (p < 0.05). In conclusion, although each manipulation individually resulted in small changes in myelination, their combined effects were more pronounced. These changes were parallel to abnormal expression levels of the molecular factors that contribute to myelination.

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Data availability

All data generated during this study are available from the corresponding author on request.

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Acknowledgements

The present article is financially supported by the Research Department of The School of Medicine, Shahid Beheshti University of Medical Sciences (Grant Number: 14666), and IR.SBMU.MSP.REC.1397. 670. The authors are thankful for this valuable support.

Funding

This study was funded by the Research Department of The School of Medicine, Shahid Beheshti University of Medical Sciences (Grant Number: 14666) and IR.SBMU.MSP.REC.1397. 670.

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Authors and Affiliations

  1. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Namvarpour, Elahe Ranaei, Abdollah Amini & Zahra Roudafshani

  2. Institute for Cognitive Sciences Students (ICSS), Tehran, Iran

    Zahra Namvarpour

  3. Central Lab, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zahra Roudafshani

  4. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Javad Fahanik-Babaei

  5. Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, 1985717443, Tehran, Iran

    Javad Fahanik-Babaei

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  1. Zahra Namvarpour
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  2. Elahe Ranaei
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  3. Abdollah Amini
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  4. Zahra Roudafshani
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  5. Javad Fahanik-Babaei
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Contributions

Z. Namvarpour & A. Amini, co-designed the study, supervised all the experiments, and analyzed the results. E. Ranaei & Z. Roudafshani participated in literature and performed the methods. A. Amini: editing manuscript and funding. J. Fahanik-Babaei wrote the original draft of the manuscript and provided laboratory materials. All authors read, modified, and approved the final version of the manuscript.

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Correspondence to Abdollah Amini.

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The Research and Ethics Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC. 1397.670) approved this research study. All experimental procedures and animal handling were conducted following the National Institute of Health “Guide for the Care and Use of Laboratory Animals”.

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Namvarpour, Z., Ranaei, E., Amini, A. et al. Effects of prenatal exposure to inflammation coupled with prepubertal stress on prefrontal white matter structure and related molecules in adult mouse offspring. Metab Brain Dis 37, 1655–1668 (2022). https://doi.org/10.1007/s11011-022-00968-9

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