Cellular neuroscienceRepeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats
Section snippets
Experimental procedures
All experiments were conducted in accordance with the Canadian Council on Animal Care guidelines and international guidelines regarding appropriate and ethical treatment of animals and were approved by the Animal Care Centre at the University of British Columbia. Every effort was made to minimize the number of animals used per group and to minimize the suffering of animals used throughout all experimental procedures.
Male rats have larger DG volumes than female rats
Overall, as expected, the volumes of the GCL and hilus of the hippocampus were larger in males than in females, and the hilus was larger than the GCL, but there were no other significant effects (main effect of sex: F1,16=15.6, P=0.001; main effect of area: F1,16=819, P<0.001; all other effects except for sex×area: P>0.40; Table 1). There was a significant sex×area interaction effect in volume (F1,16=11.0, P=0.004), post hoc tests revealed that males had larger hilar volume (P<0.001) than
Discussion
The results from the present study demonstrate that estradiol regulates cell death and neurogenesis in the hippocampus of female, but not male rats. Repeated (15-day) administration of estradiol resulted in a decrease in cell death and new neuron survival, with a slight increase in cell proliferation by the end of treatment, in the DG of adult female, but not male, rats. The finding that estradiol decreases overall cell death is consistent with previous reports demonstrating that estradiol can
Conclusion
We have reported here the first evidence of a sex difference in vivo in the effects of repeated administration of estradiol on hippocampal neurogenesis and cell death. Although repeated estradiol exposure increased cell proliferation and decreased cell death in female rats, it had no such effect in male rats. As estradiol has been presented as a potential therapeutic or preventative agent for neurodegenerative diseases, it is important to note that while both men and women suffer from such
Acknowledgments
We thank Stephanie Lieblich and Dr. Mark Spritzer for assistance with laboratory work. Funding for this research was provided by the Canadian Institutes of Health Research (LAMG). J.M.B. is the recipient of a Canadian Graduate Scholarship from the Natural Sciences and Engineering Research Council of Canada. LAMG is a Michael Smith Senior Scholar.
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