Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment

Zoubovsky, S. P.; Williams, M. T.; Hoseus, S.; Tumukuntala, S.; Riesenberg, A.; Schulkin, J.; Vorhees, C. V.; Campbell, K.; Lim, H.-W.; Muglia, L. J.

doi:10.1101/2020.05.20.106674

bioRxiv · 10.1101/2020.05.20.106674

Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment

Zoubovsky, S. P.·Williams, M. T.·Hoseus, S.·Tumukuntala, S.·Riesenberg, A.·Schulkin, J.·Vorhees, C. V.·Campbell, K.·Lim, H.-W.·Muglia, L. J.

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Abstract

Prenatal stress (PS) is associated with increased vulnerability to affective disorders. Transplacental glucocorticoid passage and stress-induced maternal environment alterations are recognized as potential routes of transmission that can fundamentally alter neurodevelopment. However, molecular mechanisms underlying aberrant emotional outcomes or the individual contributions intrauterine stress versus maternal environment play in shaping these mechanisms remain unknown. Here, we report anxiogenic behaviors, anhedonia, and female hypothalamic-pituitary-adrenal axis hyperactivity as a consequence of psychosocial PS in mice. Sex-specific placental responses to stress and evidence of fetal amygdala programming precede these abnormalities. In adult offspring, we observe amygdalar transcriptional changes demonstrating sex-specific dysfunction in synaptic transmission and neurotransmitter systems. We find these abnormalities are primarily driven by in-utero stress exposure. Importantly, maternal care changes postnatally reverse anxiety-related behaviors and partially rescue gene alterations associated with neurotransmission. Our data demonstrate the influence maternal environment exerts in shaping offspring emotional development despite deleterious effects of intrauterine stress.

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Zoubovsky, S. P., Williams, M. T., Hoseus, S., Tumukuntala, S., Riesenberg, A., Schulkin, J., Vorhees, C. V., Campbell, K., Lim, H.-W., Muglia, L. J.. 2020-05-23. Prenatal psychosocial stress-induced behavioral and neuroendocrine abnormalities are associated with sex-specific alterations in synaptic transmission and differentially modulated by maternal environment. https://doi.org/10.1101/2020.05.20.106674

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