Elsevier

Neuroscience

Volume 168, Issue 3, 14 July 2010, Pages 680-690
Neuroscience

Cognitive, Behavioral and Systems Neuroscience
Research Paper
Chronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats

https://doi.org/10.1016/j.neuroscience.2010.04.023Get rights and content

Abstract

Adult neurogenesis in the dentate gyrus of the hippocampus is altered with stress exposure and has been implicated in depression. High levels of corticosterone (CORT) suppress neurogenesis in the dentate gyrus of male rats. However both acute and chronic stress do not consistently reduce adult hippocampal neurogenesis in female rats. Therefore, this study was conducted to investigate the effect of different doses of corticosterone on hippocampal neurogenesis in male and female rats. Rats received 21 days of s.c. injections of either oil, 10 or 40 mg/kg CORT. Subjects were perfused 24 h after the last CORT injection and brains were analyzed for cell proliferation (Ki67-labeling) or immature neurons (doublecortin-labeling). Results show that in both males and females high CORT, but not low CORT, reduced both cell proliferation and the density of immature neurons in the dentate gyrus. Furthermore, high CORT males had reduced density in immature neurons in both the ventral and dorsal regions while high CORT females only showed the reduced density of immature neurons in the ventral hippocampus. The high dose of CORT disrupted the estrous cycle of females. Further, the low dose of CORT significantly reduced weight gain and increased basal CORT levels in males but not females, suggesting a greater vulnerability in males with the lower dose of CORT. Thus we find subtle sex differences in the response to chronic CORT on both body weight and on neurogenesis in the dorsal dentate gyrus that may play a role in understanding different vulnerabilities to stress-related neuropsychiatric disorders between the sexes.

Section snippets

Animals

All protocols were in accordance with ethical guidelines set by the Canada Council for Animal Care and were approved by the University of British Columbia Animal Care Committee. All efforts were made to minimize the number of animals used and their suffering. Fifteen female and fifteen male Spragueā€“Dawley rats were obtained from Charles River (Saint Constant, QC, Canada) at approximately 3 months of age. After 1 week rats were housed individually in clear polyurethane bins (48Ɨ27Ɨ20 cm3) with

High CORT significantly attenuated weight gain in males and females, while low CORT significantly attenuated weight gain in males only

Due to individual and sex differences in body weight, we analyzed percentage of weight gain or loss. We calculated this by setting the weight on the day before the 1st CORT injection as 100% and calculating the percentage gain or loss for body weight on day 22. An ANOVA revealed a significant effect of treatment (F(2,24)=42.18, P<.001) and sex (F(1,24)=6.55, P=.017) as well as an interaction effect (F(2,24)=6.04, P=.007). Subsequent post hoc analysis revealed that the high CORT dose caused a

Discussion

The current study is the first to directly compare neurogenesis in the dorsal and ventral dentate gyrus in response to different doses of CORT in both male and female rats. Here we show that high levels of corticosterone suppress cell proliferation and immature neuron survival in both male and female rats. Interestingly, while the low dose of CORT did not significantly reduce hippocampal cell proliferation or neurogenesis in either sex, males showed significantly attenuated weight gain and

Conclusion

In conclusion our results further support the notion that males and females exhibit different glucocorticoid/stress sensitivities and/or perhaps coping strategies. It is conceivable that ovarian steroids play a role in mediating the effect of chronic high levels of corticosterone on the different stages of neurogenesis and might explain the different effects of stress and/or glucocorticoids on cell proliferation and survival reported here and in other studies. Further our results suggest that

Acknowledgments

We would like to thank Stephanie Lieblich and Lucille Hoover for the help with this study. SB received a postdoctoral fellowship from the Department of Foreign Affairs and International Trade Canada. The study was supported by a NSERC grant to LAMG. LAMG is a Michael Smith Senior Scholar. The authors declare that they have no conflicts of interest.

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