Elsevier

Neuroscience

Volume 124, Issue 2, 2004, Pages 429-438
Neuroscience

Chronic corticosterone affects brain weight, and mitochondrial, but not glial volume fraction in hippocampal area CA3

https://doi.org/10.1016/j.neuroscience.2003.11.031Get rights and content

Abstract

Corticosterone (CORT), the predominant glucocorticoid in rodents, is known to damage hippocampal area CA3. Here we investigate how that damage is represented at the cellular and ultrastructural level of analyses. Rats were injected with CORT (26.8 mg/kg, s.c.) or vehicle for 56 days. Cell counts were estimated with the physical disector method. Glial and mitochondrial volume fractions were obtained from electron micrographs. The effectiveness of the CORT dose used was demonstrated in two ways. First, CORT significantly inhibited body weight gain relative to vehicles. Second, CORT significantly reduced adrenal gland, heart and gastrocnemius muscle weight. Both the adrenal and gastrocnemius muscle weight to body weight ratios were also significantly reduced. Although absolute brain weight was reduced, the brain to body weight ratio was higher in the CORT group relative to vehicles, suggesting that the brain is more resistant to the effects of CORT than many peripheral organs and muscles. Consistent with that interpretation, CORT did not alter CA3 cell density, cell layer volume, or apical dendritic neuropil volume. Likewise, CORT did not significantly alter glial volume fraction, but did reduce mitochondrial volume fraction. These findings highlight the need for ultrastructural analyses in addition to cellular level analyses before conclusions can be drawn about the damaging effects of prolonged CORT elevations. The relative reduction in mitochondria may indicate a reduction in bioenergetic capacity that, in turn, could render CA3 vulnerable to metabolic challenges.

Section snippets

Subjects

Ten male Sprague–Dawley rats (380–450 g) were habituated to the colony for 6 days and handled for an additional 5 days before treatment conditions commenced. Food and water were provided ad libitum, but monitored for the duration of the experiment. All treatment and testing protocols were approved by the institution's animal care and use committee and conformed to National Institutes of Health guidelines. All effort was made to minimize the number of animals used. Animals were well-handled

Body and organ weights

Despite the equal average body weight across groups at the beginning of treatment, the CORT group weighed less at the end of the experiment. A repeated measures ANOVA on mean body weights (with treatment as the between subjects factor and week as the within subjects factor) revealed a main effect for both treatment [F(1,8)=16.5, P<0.01; see Fig. 3] and week [F(8,64)=37.2, P<0.0001; see Fig. 3]. A significant interaction between treatment and week was also found [F(8,64)=15.9, P<0.0001; see Fig.

Discussion

Our findings indicate that elevating CORT for 56 days does not influence CA3 cell number or cell layer volume. These findings are consistent with previous studies utilizing unbiased counting methods (Vollmann-Honsdorf et al., 1997, Sousa et al., 1998, Leverenz et al., 1999). The dose used in the present study caused no reduction in the volume of the dorsal CA3 apical dendritic neuropil. Whereas we expected to see an increase in glial volume fraction, we did not find that in this study. Either

Conclusion

CORT elevations that were sufficient to reduce organ and muscle weight as well as significantly reduce brain weight, caused no gross anatomical alterations in the middle and proximal regions of dorsal CA3. Although CORT has been shown to reduce GFAP, glial volume fraction was not significantly reduced after exposure to elevated CORT for 56 days. In contrast, CORT reduced mitochondrial volume fraction, suggesting that metabolic capacity may be impaired. Because indications of damage were

Acknowledgements

We would like to thank Joe Fenstermacher for the generous use of his ultramicrotome. We would like to thank Rachel Encarnacion, Noriko Kawashima, Rabia Razi, Baynazier Ansari and Diana Lawrence for help handling animals, monitoring food and water, and collecting data. Glenn Hudson, Ralph Molaro and Robert Chorley have generously given their time to develop and maintain equipment used for this project.

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