Female early adult depression results in detrimental impacts on the behavioral performance and brain development in offspring

Abstract

Aims: The present study was to understand whether early adult depressive females implicated their offspring.

Methods: Seven-week-old female mice were subject to chronic mild stress (CMS) to establish the animal model of depression. The behavioral performance of their offspring were tested via neonatal reflexes tests, hole-board test, and morris water maze test in different ages. Astrocyte number, hippocampal volume, and neurogenesis were analyzed via immunohistochemical blotting. Glucocorticoid receptor (GR) expression and serum cortisol levels were measured by western blotting and ELISA.

Results: Female depressive mice had normal fertility, but their offspring had lowered neonatal survival rate and body weight from neonatal period to early adulthood. The offspring of female depressive mice exhibited the impairments of neonatal reflex attainment and memory, but had higher emotionality as adults. Furthermore, the astrocyte number, hippocampal volume, and neurogenesis were reduced in the offspring. However, the expressions of GR were increased in the hippocampus of offspring.

Conclusion: This study reveals that female early adult depressive mice have normal reproductive ability, but make long-term detrimental impacts on the behavioral performance and brain development of their offspring.

Figure 1

Effect of CMS on sucrose intake (A) and sucrose preference (B), TST immobility time (C), and body weight (D) of female adolesent mice. CMS procedure significantly decreased the sucrose preference and sucrose intake of female mice (A, B), and increased the immobility time in TST (C). Under normal condition, the body weight of females in week 6 was significantly heavier than that in week 0, but no significant difference of body weight was observed between week 0 and week 6 of CMS group (D). Data represent the mean ± SEM. **P < 0.01, *P < 0.05 versus control group; ##P < 0.01 versus control in week 0.

Figure 2

The effect of female early adult depressive mice on the offspring's body weights (A), neonatal reflexes (B), and hangwire (C). Offspring of depressive mice showed significant decreases in body weights from PND 0 to PND 63. But no difference in body weights between the two offspring groups in PND75 (A) was observed. Offspring of depressive mice significantly increased the time of righting reflex (B) and decreased the time of hangwire (C). No significant difference was found between the two offspring groups in the time of cliff avoidance (B). Data represent the mean ± SEM. **P < 0.01, *P < 0.05 versus offspring of control groups.

Figure 3

Offspring's performance in Morris water maze (MWM) test on the spatial memory acquisition and retention (A‐D), hole‐board (HB) test (E, F), sucrose preference and forced swimming test (FST) (G, H). MWM learning curves showed that, in the 5 days of training, all offspring mice were capable of accomplishing the escape task, with the escape latency of offspring from depressive groups shorter than that of offsrping from control groups (A). No difference was observed in the two progeny groups in swimming speed (B). In addition, figure C and D showed the effect of maternal depression on the performance of the offspring in probe test of MWM test, which showed significant increased times of escape latency (C) and decreased times of crossed platform (D) in offspring of depressive groups. Besides, offspring of the depressive mice showed the increases of latency to headdipping (E) and decreases of head dip/head sniff ratio (F) in HB test. No significant difference of the immobility time in FST (G) and the sucrose preference (H) was found between the two offspring groups. Data represent the mean ± SEM. **P < 0.01, *P < 0.05 versus offspring of control groups.

Figure 4

Effect of female early adult depressive mice on the cell proliferation in SGZ of offspring. Offspring of depressive mice showed significant inhibition of cell proliferation in SGZ from PND 7 to PND 75, and showed a decreased about 51%, 39%, and 13% in offspring compared to the progeny of control groups. But no difference was found in the two offspring groups on PND 3. The number of Brdu positive cells of control progeny on PND 7 was higher than that on PND3, which wasn't be shown in offspring of depressive group. Brdu: 5‐bromo‐2‐deoxyuridine. Data represent the mean ± SEM. **P < 0.01, *P < 0.05 versus offsping of control groups; ##P < 0.01, versus offspring of control groups on PND 3. Scale bar, 55 μm.

Figure 5

Effect of female early adult depressive mice on the glial fibrillary acidic protein (GFAP) positive cells number in hippocampus (A, B) and the hippocampal volume (C) of offspring. Hippocampal volumetry revealed that a significant reduce in GFAP positive cells in offspring of depressive mice on PND 75 (29%) (A, B), and in hippocampal volume on PND 75 (10%) (C). But no difference was detected between the two offspring groups on PND 3, PND 7, and PND 28. Data represent the mean ± SEM. **P < 0.01, *P < 0.05 versus offspring of control groups. Scale bar, 55 μm.

Figure 6

Effect of early adult depression on the serum corticosterone level in maternal and offspring blood (A, B) and on the expressions of GR in offspring and offspring hippocampus (C, D). CMS procedure caused a 2.4‐fold rise in serum corticosterone in CMS group maternal mice (A), but no difference was detected between CMS and control group on the relative level of GR/β‐actin (C). C: Control, M: CMS, *P < 0.05 versus control group. Serum corticosterone levels in offspring of depressive mice was around 68% of that in offspring of control groups on PND28 but no difference was detected between the two offspring groups on PND75 (B). Relative level of GR/β‐actin in hippocampus of offspring from depressive groups was higher than that in offspring from control groups on PND7, 28, and 75, but no difference was detected between the two offspring groups on PND3 (D). C: offspring of control groups, M: offspring of depressive groups, *P < 0.05 versus offspring of control groups. Data represent the mean ± SEM.