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. 2016 Dec 1;39(12):2211-2221.
doi: 10.5665/sleep.6328.

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects

Olena Santangeli  1 , Henna Lehtikuja  1 , Eeva Palomäki  1 , Henna-Kaisa Wigren  1 , Tiina Paunio  2 , Tarja Porkka-Heiskanen  1
Affiliations

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects

Olena Santangeli et al. Sleep. .

Abstract

Study objective: Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood.

Methods: Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and BDNF gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood. Spontaneous sleep, sleep homeostasis, and BF extracellular adenosine levels were assessed in adulthood.

Results: CF rats demonstrated increased number of REM sleep onsets in light and dark periods of the day. Total REM and NREM sleep duration was also increased during the light period. While sleep homeostasis was not severely affected, basal level of adenosine in the BF of both male and female CF rats was lower than in controls. CF did not lead to considerable changes in behavior.

Conclusions: Even when the consequences of adverse early-life events are not observed in tests for anxiety and depression, they leave a molecular mark in the brain, which can act as a vulnerability factor for psychopathologies in later life. Sleep is a sensitive indicator for even mild early-life stress.

Keywords: BDNF; adenosine; cross-fostering; depression; sleep homeostasis.

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Figures

Figure 1
Figure 1
Schematic representation of the timeline of the experiments. OF, open field test; SPT, sucrose preference test; CTRL, control rats; CF, cross-fostering rats.
Figure 2
Figure 2
(A) Vigilance state distribution through light-dark period and (B) number of REM sleep onsets in CTRL and CF male and female rats during BL day. Males (n = 7/control group, n = 6/CF group), females (n = 5/CTRL group, n = 5/CF group). # Difference is significant between CTRL and CF rats (factorial ANOVA (factors: sex and treatment), P < 0.05). *Difference is significant between CTRL and CF rats within same-sex group (one-way ANOVA, P < 0.05). CTRL, control rats; CF, cross-fostering rats; BL, baseline day.
Figure 3
Figure 3
(A) NREM and (B) REM sleep duration in CTRL and CF male and female rats during recovery hours (16:00–21:00) after SD. Males (n = 7/control group, n = 6/CF group), females (n = 5/CTRL group, n = 5/CF group). # Difference is significant between BL and SD days (factorial repeated measures ANOVA (between subject factors: sex and treatment, within-subject factor: SD), P < 0.05). *Difference is significant between BL and SD days within same-sex, same-treatment group (one-way ANOVA, P < 0.05). CTRL: control rats. CF, cross-fostering rats; BL, baseline day; SD, sleep deprivation.
Figure 4
Figure 4
NREM sleep delta (1.08–3.79 Hz) power in CTRL and CF male and female rats during one-hour recovery sleep (16:00–17:00) after SD. Males (n = 7/control group, n = 6/CF group), females (n = 5/ CTRL group, n = 5/CF group). While there is a significant increase in NREM sleep delta power after SD (factorial repeated measures ANOVA (between subject factors: sex and treatment, within-subject factor: SD), P < 0.05) for both females and males (about 50% and 20%, respectively), there is no difference between CTRL and CF rats. CTRL, control rats. CF, cross-fostering rats; BL, baseline day; SD, sleep deprivation.
Figure 5
Figure 5
Baseline adenosine concentration (nM) in CTRL and CF male and female rats in the basal forebrain. Males: n = 7/CTRL group, n = 6/CF group, females: n = 5/CTRL group, n = 5/CF group. *Difference is significant between CTRL and CF rats within same-sex group (oneway ANOVA, P < 0.05). CTRL, control rats; CF, cross-fostering rats; BF, basal forebrain.
Figure 6
Figure 6
BDNF gene expression in the basal forebrain, frontal cortex and hypothalamus in male and female rats during adolescence and adulthood. Males: n = 5/CTRL group, n = 6/CF group, females: n = 6/CTRL group, n = 6/CF group. In the basal forebrain, BDNF gene expression level was higher in adolescence than in adulthood (factorial ANOVA (factors: sex, age and treatment), P < 0.05) and tended to be lower in CF rats than in CTRLs (factorial ANOVA (factors: sex, age and treatment), P = 0.08). Such differences were not observed in other brain areas. CTRL, control rats; CF, cross-fostering rats.
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