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Got milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats

Molecular Psychiatry volume 27, pages 4829–4842 (2022)Cite this article

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Abstract

Previous studies have underscored the importance of breastfeeding and parental care on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we investigated how lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 affects maternal care, milk, and offspring development. MIA was associated with elevated milk corticosterone concentrations on P10, which recovered by P11. In contrast, both milk triglyceride and percent creamatocrit values demonstrated a prolonged decrease following inflammatory challenge. Adolescent MIA offspring were heavier, which is often suggestive of poor early life nutrition. While MIA did not decrease maternal care quality, there was a significant compensatory increase in maternal licking and grooming the day following inflammatory challenge. However, this did not protect against disrupted neonatal huddling or later-life alterations in sensorimotor gating, conditioned fear, mechanical allodynia, or reductions in hippocampal parvalbumin expression in MIA offspring. MIA-associated changes in brain and behavior were likely driven by differences in milk nutritional values and not by direct exposure to LPS or inflammatory molecules as neither LPS binding protein nor interleukin-6 milk levels differed between groups. These findings reflected comparable microbiome and transcriptomic patterns at the genome-wide level. Animal models of early life stress can impact both parents and their offspring. One mechanism that can mediate the effects of such stressors is changes to maternal lactation quality which our data show can confer multifaceted and compounding effects on offspring physiology and behavior.

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Fig. 1: Maternal care and offspring huddling behaviors following maternal immune activation (MIA) during the mid-lactational period.
Fig. 2: Nutritional profile and microbiome community distribution of milk following maternal immune activation (MIA) during the mid-lactational period.
Fig. 3: Transcriptomic analyses of milk samples obtained on P10 from rat mothers exposed to either saline or maternal immune activation (MIA).
Fig. 4: Transcriptomic analyses of milk samples obtained on P11 from rat mothers exposed to either saline or maternal immune activation (MIA).
Fig. 5: Adolescent offspring physiology and behavior following maternal immune activation (MIA) during the mid-lactational period.
Fig. 6: Summary of mechanisms affecting milk quality and offspring brain and behavior following maternal immune activation (MIA) during the mid-lactational period.

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Acknowledgements

The authors would like to thank the MCPHS Schools of Pharmacy and Arts & Sciences for their continual support, the Bioinformatic Resource Center at the Rockefeller University where the RNA-seq was performed, and the University of Massachusetts Boston where HD is a graduate student. Figure 6 was made with BioRender.com and an earlier version of this manuscript was posted on the preprint server bioRvix. The content is solely the responsibility of the authors and does not necessarily represent the official views of any of the financial supporters.

Funding

This project was funded by NIMH under Award Number R15MH114035 (to ACK) and the Massachusetts College of Pharmacy and Health Sciences (MCPHS) Center for Undergraduate Research (H.T).

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Authors and Affiliations

  1. School of Arts & Sciences, Health Psychology Program, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, 02115, US

    Holly DeRosa, Hieu Tran & Amanda C. Kentner

  2. Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Ave, New York, NY, 10065, US

    Salvatore G. Caradonna & Jordan Marrocco

  3. Department of Biology, Touro University, 227W 60th St, New York, NY, 10023, US

    Jordan Marrocco

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  1. Holly DeRosa
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Contributions

H.D., S.G.C., H.T., and A.C.K., ran the experiments; H.D., S.G.C., J.M., & A.C.K. analyzed and interpreted the data; H.D. and A.C.K. wrote the manuscript; A.C.K., designed and supervised the study.

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Correspondence to Amanda C. Kentner.

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DeRosa, H., Caradonna, S.G., Tran, H. et al. Got milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats. Mol Psychiatry 27, 4829–4842 (2022). https://doi.org/10.1038/s41380-022-01744-y

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