Developmental changes in desensitisation of c-Fos expression induced by repeated maternal separation in pre-weaned mice.
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.
Department of Anatomy and Cell Biology, Nara Medical University, Kashihara, Nara, Japan.
N
N
Horii-Hayashi
T
T
Sasagawa
W
W
Matsunaga
Y
Y
Matsusue
C
C
Azuma
M
M
Nishi
D000223:Adaptation, Psychological / Q000502:physiology*; D000818:Animals; D000833:Animals, Suckling; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005260:Female; D048788:Growth and Development / Q000502:physiology*; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D014886:Weaning
D016760:Proto-Oncogene Proteins c-fos; D003345:Corticosterone