Biomedical subjects

D P McCloskey

Publications and source records attributed to D P McCloskey.

4 recordsLinked to original sources

PubMed2004

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.

Animals↗

PubMed2003

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.

Animals↗

PubMed2001

Exercise increases metabolic capacity in the motor cortex and striatum, but not in the hippocampus.

Acute bouts of exercise have been shown to produce transient increases in regional cerebral glucose utilization, oxygen uptake, and cerebral blood flow in motor cortex, striatum, and hippocampus. The purpose of this study was to determine whether or not chronic exercise will cause long-term metabolic plasticity in brain structures activated during physical activity. The activity of cytochrome oxidase (COX), is coupled to the production of ATP, and reflects long-term plasticity in metabolic capacity. The present study examined whether or not 6 months of voluntary exercise would increase COX activity in the striatum, sensorimotor cortex, and three hippocampal subfields. Five-month-old, female Long-Evans hooded rats were randomly assigned to a control or exercise condition. Exercising rats had running wheels attached to their home cages. After the training period, fresh brains were rapidly frozen and sectioned with a cryostat. COX activity was measured using COX histochemical methods and optical densitometry. Rats in the exercise condition had significantly higher optical density in the hindlimb and forelimb motor cortices (18%, P<0.01) and dorsolateral caudate putamen (17%, P<0.01), but not in the ventrolateral caudate putamen or any subfield of the hippocampus. Although exercise is believed to increase neuronal activity in the hippocampus, motor cortex and striatum, only limb representations in the motor cortex and striatum increase bioenergetic capacity after regular exercise.

Animals↗

PubMed2000

Exercise influences spatial learning in the radial arm maze.

Previous studies indicate that the hippocampus is active during exercise, and that neurotrophin expression, receptor density, and survival of dentate gyrus granule cells in the hippocampus can be modified by moderate voluntary exercise. The present study was designed to test the consequences of voluntary exercise on a hippocampal-related behavior. Exercising and control rats were tested on the standard and delayed nonmatch-to-position (DNMTP) version of the eight-arm radial maze, both of which are sensitive to hippocampal damage. Voluntarily exercising rats ran in running wheels attached to their home cage for 7 weeks prior to and throughout testing, and took 30% fewer trials to acquire criterion performance than sedentary controls. Both groups spent the same average time per arm. Once the eight-arm maze had been learned to criterion, group differences were not apparent. Exercise can facilitate acquisition of a hippocampal-related spatial learning task, but does not affect performance following acquisition. Further work will be necessary to link these effects to hippocampal-related variables shown to be influenced by exercise.

Analysis of Variance↗