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

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.

Early life stress induces sex‐dependent increases in phosphorylated extracellular signal‐regulated kinase in brains of mice with neuropathic pain

“…The present observations suggest that MSSI increases p‐ERK expression in multiple brain regions under conditions of basal or neuropathic pain. In agreement, previous studies demonstrate that maternal separation increase p‐ERK expression in the amygdala (Park et al., ), and that the immediate early gene product and marker of activated neurons c‐fos was increasingly expressed in multiple brain regions following exposure to maternal separation (Horii‐Hayashi et al., ). Hence, early life stress activates neuronal function in multiple brain regions.…”

“…In our study, mice were stimulated by light touch under non‐anaesthetized conditions, which may have influenced brain p‐ERK expression. Furthermore, maternal separation was previously shown to induce p‐ERK expression in the amygdala, and c‐fos expression in multiple brain regions without light touch stimulation (Horii‐Hayashi et al., ; Park et al., ). Therefore, although brain p‐ERK expression is not correlated with pain sensitivity, neuronal activity in several brain regions is elevated by MSSI.…”

“…Previous studies have demonstrated that the increased neuronal activity in the forebrain leads to the enhancement of inflammatory and neuropathic pain (Wei et al., ; Descalzi et al., ). Moreover, early life stress impairs the neuronal activity in the forebrain which is associated with the development of behavioural abnormalities (Baudin et al., ; Goff et al., ; Horii‐Hayashi et al., ; Malter Cohen et al., ). From these findings, we hypothesized that early life stress negatively affect the neuropathic pain mediated by the changes in the neuronal function in the forebrain.…”

Stress and the Reproductive Axis

“…Even natural variations in the quality or quantity of maternal care can have a long-term impact on offspring brain and behaviour. Human epidemiological and animal experimental studies show that early social experiences influence the functioning of physiological processes even into adulthood (3,(16)(17)(18)(19)(20)(21)(22).…”

Transcriptomic signatures of social experience during early development in a highly social cichlid fish

“…Kasumovic & Brooks, ). However, information on gene expression changes influencing phenotypic development during ontogeny remains scarce (Horii‐Hayashi et al, ; Schmidt et al, ; Vazquez et al, ). Using a time series approach, we showed that in the cichlid fish Neolamprologus pulcher social experience influences whole‐brain gene expression during a stage when these fish have already developed a social behaviour repertoire (see Arnold & Taborsky, ) and are at the verge of becoming brood care helpers (Kasper et al, ).…”