The impact of early-life stress on the expression of HPA-associated genes in the adult murine brain

in Behaviour
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Early life is an important period for the development of the nervous system and for the programming of behavioural phenotypes in adulthood. In our study, two types of early-life stress were used: prolonged separation of pups from their mothers (for 3 h/day, maternal separation (MS)) and brief separation (for 15 min/day, handling (HD)). We analysed the effects of early-life stress on behaviour and the expression of HPA-associated genes in the hypothalamus, hippocampus, and frontal cortex of male mice. Adult mice in the MS group demonstrated reduced locomotor activity and deficiencies in spatial long-term memory, while the HD showed no significant changes. Additionally, early-life MS resulted in reduced hippocampal Crhr1 mRNA, increased MR/GR mRNA in the hippocampus and hypothalamus. Both groups, HD and MS, showed increased Avp mRNA in the hypothalamus. Thus, prolonged maternal separation but not brief leads to adverse behavioural changes and influences the expression of HPA-associated genes in a brain region-specific manner.

The impact of early-life stress on the expression of HPA-associated genes in the adult murine brain

in Behaviour



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    Experiment design: C57BL/6 strain mice were exposed to two types of early-life stress on PND 2 through 14 (HD for 15 min once a day; MS for 3 h once a day). All offspring were weaned from their mother on PND 30. Each of the three groups (NC, HD and MS) was divided into two subgroups. One was exposed to an open-field test, after which tissues were collected. The other was given the MWM only. n is the number of animals in each group used in these experiments.

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    Sets of primers.

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    Behavioural parameters in the open-field test. (A) Total activity (% of total time); (B) distance travelled (total length of the path travelled in cm); (C) time spent in the centre (% of total time); (D) heat maps showing mouse trajectories (the black line indicates the actual trajectory of all animals of each group during the test). Data are presented as mean ± SEM (white bar, NC; grey bar, HD; black bar, MS); ** p<0.01, compared with the NC group; # p<0.05; ## p<0.01, compared with the HD group (Fisher’s LSD as post hoc).

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    Behavioural parameters in the MWM test. (A) Latency (in s) to find the platform in each of the 16 trials; (B) time spent in the sectors (time spent in each of the 4 sectors as a percentage of total time). Data are presented as mean ± SEM; * p<0.05; ** p<0.01, compared with Target sector time; # p<0.05, compared with the HD group (Fisher’s LSD as post hoc).

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    Physiological parameters: Serum corticosterone level (ng/ml) and adrenal index (mg/g). Data are presented as mean ± SEM (white bar, NC; grey bar, HD; black bar, MS).

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    Avp, Crh and Crhr1 mRNA levels: Data are presented as mean ± SEM (white bar: NC; grey bar: HD; black bar: MS); Hyp, hypothalamus; Hipp, hippocampus; Fc, frontal cortex. * p<0.05, compared with the NC group; ## p<0.01, compared with the HD group (Fisher’s LSD as post hoc).

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    GR, MR and MR/GR mRNA levels: Data are presented as mean ± SEM (white bar: NC; grey bar: HD; black bar: MS); Hyp, hypothalamus; Hipp, hippocampus; Fc, frontal cortex. ** p<0.01, compared with the NC group (Fisher’s LSD as post hoc).

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    Fkbp4, Fkbp5 and Fkbp4/Fkbp5 mRNA levels: Data are presented as mean ± SEM (white bar: NC; grey bar: HD; black bar: MS); Hyp, hypothalamus; Hipp, hippocampus; Fc, frontal cortex.

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