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

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.

Chronic administration of corticosterone impairs spatial reference memory before spatial working memory in rats.

Corticosterone (CORT), the predominant glucocorticoid in rodents, elevated for 21 days damages hippocampal subregion CA3. We tested the hypothesis that CORT would impair spatial memory, a hippocampal function. In each of the three experiments, rats received daily, subcutaneous injections of either CORT (26.8 mg/kg body weight in sesame oil) or sesame oil vehicle alone (VEH). CORT given for 21 or 56 days effectively attenuated body weight gain and reduced selective organ and muscle weights. All behavioral testing was done on tasks that are minimally stressful and avoid deprivation. For each experiment, testing commenced 24h after the last injection. CORT given for 21 days did not impair spatial working memory in the Y-maze (Experiments 1 and 2). After 56-day administration of CORT, spatial working memory was impaired in the Y-maze (Experiment 2). CORT given for 21 days also failed to impair spatial working memory in the Barnes maze (Experiment 3). However, in trials that depended solely on reference memory, the VEH group improved in performance, whereas the CORT group did not. In conclusion, CORT elevated over a period of 21 days did not impair spatial working memory, but impaired the formation of a longer-term form of memory, most likely reference memory. Impairments in spatial working memory are seen only after longer durations of CORT administration.

A new method for the investigation of capillary structure.

Numerous physiological conditions as well as behavioral conditions have been shown to influence central nervous system vascular structure. Many of the methods used to investigate these structural alterations take advantage of the visibility of viscous substances (e.g. India ink in gelatin) perfused into the vasculature. The high viscosity of the solution, however, can cause incomplete vessel perfusion. The aim of the present study was to test whether or not capillaries seen in tissue perfused with fixative, embedded in celloidin and stained with Methylene Blue-Azure II (n=6) could be a useful alternative for the investigation of brain vascular structure. The method was compared to tissue from six rats perfused with India ink in gelatin and stained with cresyl violet. Qualitatively, vessels in the standard perfused tissue embedded in celloidin yielded clear vessels with stained pericytes. The two methods did not differ in branch point to cell ratio, length of individual capillaries, vessel length per mm(3), and capillary tortuosity. The capillary diameter was greater in the celloidin embedded tissue than in the India ink perfused tissue. Measuring the diameter between vessel walls appears to provide a more accurate measure than the widest distance between India ink pigments. Quantitative comparisons suggest that perfusion with standard fixative followed by embedding in celloidin provides vascular quantification comparable to that from India ink perfused tissue. The present method has several advantages, which include visualization of pericytes, increased probability of complete perfusion, clear view of cells that might otherwise be obscured by opaque vessels, and the possibility of using the alternate cerebral hemisphere for investigation of vascular ultrastructure.