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Long-lasting effects of prenatal stress on HPA axis and inflammation: A systematic review and multilevel meta-analysis in rodent studies

Creutzberg, K. C. and Sanson, A. and Viola, T. W. and Marchisella, F. and Begni, V. and Grassi-Oliveira, R. and Riva, M. A.

Neurosci Biobehav Rev (2021) 127: 270–283

DOI: 10.1016/j.neubiorev.2021.04.032

Abstract

Exposure to prenatal stress (PNS) can lead to long-lasting neurobiological and behavioral consequences for the offspring, which may enhance the susceptibility for mental disorders. The hypothalamus-pituitary-adrenal (HPA) axis and the immune system are two major factors involved in the stress response. Here, we performed a systematic review and meta-analysis of rodent studies that investigated the effects of PNS exposure on the HPA axis and inflammatory cytokines in adult offspring. Our analysis shows that animals exposed to PNS display a consistent increase in peripheral corticosterone (CORT) levels and central corticotrophin-releasing hormone (CRH), while decreased levels of its receptor 2 (CRHR2). Meta-regression revealed that sex and duration of PNS protocol are covariates that moderate these results. There was no significant effect of PNS in glucocorticoid receptor (GR), CRH receptor 1 (CRHR1), pro- and anti-inflammatory cytokines. Our findings suggest that PNS exposure elicits long-lasting effects on the HPA axis function, providing an important tool to investigate in preclinical settings key pathological aspects related to early-life stress exposure. Furthermore, researchers should be aware of the mixed outcomes of PNS on inflammatory markers in the adult brain.

Citation

Creutzberg, K. C., Sanson, A., Viola, T. W., Marchisella, F., Begni, V., Grassi-Oliveira, R., & Riva, M. A. (2021). Long-lasting effects of prenatal stress on HPA axis and inflammation: A systematic review and multilevel meta-analysis in rodent studies. Neurosci Biobehav Rev, 127, 270–283. https://doi.org/10.1016/j.neubiorev.2021.04.032 Cytokines, Meta-analysis, Hpa, Prenatal stress

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