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Stress in utero alters neonatal stress-induced regulation of the synaptic plasticity proteins Arc and Egr1 in a sex-specific manner

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Abstract

The present study in juvenile rats investigated a “two-hit model” to test the impact of prenatal stress exposure (“first hit”) on the regulation of the synaptic plasticity immediate early genes Arc and Egr1 in response to a second neonatal stressor (“second hit”) in a sex-specific manner. Three stress-exposed animal groups were compared at the age of 21 days in relation to unstressed controls (CON): preS animals were exposed to various unpredictable stressors during the last gestational trimester; postS animals were exposed to 45 min restraint stress at postnatal day 21, pre/postS animals were exposed to a combination of pre- and postnatal stress as described for the two previous groups. The postS and pre/postS groups were killed 2 h after exposure to the postnatal stressor, males and females were separately analyzed. In line with our hypothesis we detected sex-specific stress sensitivity for both analyzed proteins. Males did not show any significant changes in Arc expression irrespective of the stress condition. In contrast, females, which had been pre-exposed to prenatal stress, displayed an “amplified” Arc upregulation in response to postnatal stress (pre/postS group) compared to unstressed controls, which may reflect a “sensitization” effect of prenatal stress. For Egr1, the females did not show any stress-induced regulation irrespective of the stress condition, whereas in males, which were pre-exposed to prenatal stress, we observed a “protective” effect of prenatal stress on postnatal stress-induced downregulation of Egr1 expression (pre/postS group), which may indicate that prenatal stress exposure may induce “resilience”.

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Fig. 1
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Abbreviations

ADHD:

Attention deficit hyperactivity disorder

Arc:

Activity-regulated cytoskeleton-association protein

DAB:

3,3′-diaminobenzidine hydrochloride

Egr1:

Early growth response protein

PND:

Postnatal day

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Acknowledgments

This research was supported by grants from the German Science Foundation (INST 272/224-1 FUGG), Bundesministerium für Bildung und Forschung (BMBF) TRANSGEN/UBICA, BMBF/TÜBITAK TUR 10/I48, the Center of Behavioral Brain Sciences (CBBS) and the European Regional Development Fund (ERDF).

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Correspondence to Nicole Gröger.

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N. Gröger, J. Bock, G. Poeggel, and K. Braun contributed equally to this work.

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Gröger, N., Bock, J., Goehler, D. et al. Stress in utero alters neonatal stress-induced regulation of the synaptic plasticity proteins Arc and Egr1 in a sex-specific manner. Brain Struct Funct 221, 679–685 (2016). https://doi.org/10.1007/s00429-014-0889-3

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  • DOI: https://doi.org/10.1007/s00429-014-0889-3

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