Cognitive, Behavioral and Systems NeuroscienceResearch PaperChronic high corticosterone reduces neurogenesis in the dentate gyrus of adult male and female rats
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 SpragueāDawley 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 (48Ć27Ć20 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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