ABSTRACT
【Objective】 To explore the role of environmental enrichment (EE) in paternal stress-induced anxiety and depression-like behaviors in offspring and its potential mechanisms. 【Methods】 Male C57BL/6 mice (F0) were treated with unpredictable chronic mild stress (UCMS) and subsequently mated with normal females to obtain F1 offspring mice. The standard environment (SE) and enriched environment (EE) were administered to F1-UCMS offspring mice during their early life (3-5 weeks of age). Anxiety-like behaviors were detected by open field test (OFT) and elevated plus-maze test (EPM); depression-like behaviors were detected via forced swimming test (FST) and sucrose preference test (SPT) at the age of 8 weeks. The expressions of LIM and SH3 domain protein 1 (LASP1) in the hippocampus of adult F1 offspring mice were detected by Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. 【Results】 Compared to F1 offspring of normal paternal (F1-Nor), F1 offspring mice of the stressed paternal (F1-UCMS) showed significantly anxiety-like behavior with reduced percentage of time spent in the central region of OFT and in the open arm of EPM (P<0.05); mice from the F1-UCMS group showed a significantly increased percentage of immobility in FST and a reduced percentage of sugar consumption in SPT (P<0.01), which demonstrated significant depression-like behaviors. Compared to the SE group, mice in the EE group had an increased percentage of time spent in the central region of the OFT [males: (7.44±0.75)% vs. (14.93±1.74)%, P<0.01; females: (8.89±1.06)% vs. (15.10±1.82)%, P<0.05] and an increased percentage of time in the open arm of EPM [males: (8.09±1.05)% vs. (14.15±1.88)%, P<0.05; females: (9.13±1.14)% vs. (14.04±1.37)%, P<0.05]. This indicated that EE ameliorated anxiety-like behavior in F1-UCMS mice with paternal stress. Compared to the SE group, mice in the EE group had an decreased percentage of immobility in FST [males: (58.63±4.51)% vs. (42.15±3.81)%, P<0.05; females: (57.96±4.19)% vs. (43.25±4.22)%, P<0.05] and an increased percentage of sugar consumption in SPT [males: (50.38±3.47)% vs. (70.39±3.12)%, P<0.01; females: (52.42±2.84)% vs. (69.99±3.55)%, P<0.01]. This indicated that EE ameliorated depression-like behavior in F1-UCMS mice with paternal stress. Hippocampal LASP1 expression was reduced in SE group compared to F1-Nor group (males: P<0.01; females: P<0.05), while LASP1 was increased in EE group compared to SE group (P<0.05) detected by RT-qPCR and Western blotting. 【Conclusion】 EE ameliorates paternal stress-induced anxiety and depression-like behaviors in F1-UCMS mice, and the mechanism may be associated with increased hippocampal LASP1 expression in F1-UCMS mice.
ABSTRACT
Objective: To investigate the antidepressant roles of estrogen in the perimenopausal depression rat model and po- tential mechnisms. Methods: The perimenopausal depression rat model was performed by ovariectomized(OVX)rat following unpre- dictable chronic mild stress(UCMS). The rats were divided into 6 groups:the control group(CON),OVX group,model (OVX+UC- MS)group,estrogen(estradiol,E2)treatment group,escitalopram group(ESC),and OVX+E2 group. Open filed and sucrose prefer- ence tests were used to investigate depression-like behavior. Nissl staining was used to analyze neuron numbers in the dentate gyrus (DG)region of rat hippocampus,Levels of 5-HT,5-H1AA, norepinephrine(NE)and dopamine(DA)in the hippocampus were deter- mined by the HPLC method,while the levels of several markers associated with HPA axis were determined by ELISA. Results: OVX+ UCMS decreased the number of crosses and rearings in open field test and decreased sucrose preference in sucrose preference test in the perimenopausal depression rat model. E2 treatment could reverse the depression behavior. E2 treatment also reversed the de- creased neuron numbers of DG region in the rat hippocampus and decreased monamine transmitter and high hypothalamic-pituitary-ad- renal axis(HPA)activation. Conclusion: E2 plays antidepressant roles in perimenopausal depression rat model through protecting neuron,increasing monamine transmitter level and decreasing HPA axis activation.