Developmental Changes in Desensitisation of c-Fos Expression Induced by Repeated Maternal Separation in Pre-Weaned Mice

N. Horii‐Hayashi,T. Sasagawa,W. Matsunaga,Y. Matsusue,C. Azuma,M. Nishi

Published 2013 in Journal of neuroendocrinology

ABSTRACT

Early‐life stress has long‐lasting effects on neuroendocrine and behaviour in adulthood. Maternal separation (MS) is used as a model of early‐life stress and daily repeated MS (RMS) for 3 h during the first two postnatal weeks is widely used in rodent studies. However, it is not fully understood whether early‐life animals desensitise/habituate to repeated stress. In the present study, we investigated the effects of daily RMS for 3 h and acute/single time MS (SMS) for 3 h on the plasma corticosterone level and c‐Fos expression in the brain in mice at different postnatal ages. Mice were subjected to: (i) RMS from postnatal day (PND) 1 to 14 (RMS14); (ii) RMS from PND14 to 21 (RMS21); (iii) SMS on PND14 (SMS14); and (iv) SMS on PND21 (SMS21). Plasma corticosterone and c‐Fos expression were examined on the final day in each experiment. The basal corticosterone levels in RMS14 and RMS21 were equal to those in respective age‐matched controls. After the final separation, the levels were significantly increased and were comparable with those after SMS14 and SMS21, respectively. Histological analysis indicated that c‐Fos expression significantly increased in many brain regions, including the paraventricular nucleus, prefrontal cortex, hippocampus, and basolateral and medial amygdale in both SMS14 and SMS21 mice. However, c‐Fos expression in RMS14 mice significantly increased in many regions, whereas such increases were hardly seen in RMS21 mice. These results indicate that repeated early‐life stress neither increases basal corticosterone, nor decreases the magnitude of the corticosterone response during the first three postnatal weeks, although desensitisation of c‐Fos expression induced by repeated stress is changed during postnatal development.

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