Dexamethasone exacerbates spatial acquisition deficits after traumatic brain injury in rats

Abstract

Objectives: Given after traumatic brain injury (TBI), Dexamethasone (DXM) reduces cerebral edema but impairs retrograde memory. This study was designed to test the hypothesis that administration of DXM to rats with TBI promotes learning deficits that are correlated with the morphological changes of hippocampal pyramidal neurons.

Methods: Adult male Wistar rats were subjected to fluid percussion injury (FPI), received DXM (5 and 10 mg/kg), and then trained for spatial acquisition. Brain sections were examined by H.E. and Golgi impregnation to quantitatively measure the morphological changes of hippocampal pyramidal neurons.

Results: The latency and path length were significantly higher in rats with FPI than those in control groups, particularly in rats receiving post-trauma high-dose DXM. At the same time, Golgi impregnation revealed a significant decrease in the number of apical and basal dendrites of pyramidal neurons of ipsilateral hippocampus in rats after injury, but the decrease was greatest of CA3 pyramidal neurons of ipsilateral hippocampus in injured rats that also received high-dose DXM.

Discussion: These findings indicate that the administration of high-dose DXM after TBI could worsen the dendritic atrophy of hippocampal CA3 pyramidal neurons and, as a result, exacerbate spatial acquisition deficits.     

Diet-induced obesity and spatial cognition in young male rats

Abstract

Recent work suggests that obesity may adversely affect cognitive behavior. To examine this suggestion, the effects of feeding a standard chow diet, and either supplemental sugar or fat on the development of obesity and performance on a test of spatial learning, the Morris Water Maze (MWM), were assessed in young male Long–Evans rats. Rats given access to a sucrose solution or dietary fat in addition to the chow diet consumed approximately 10% more calories per day, gained more weight, and had larger epididymal fat pads than rats fed the chow diet alone. Moreover, rats fed the supplemental sucrose took significantly more time to find a hidden platform in the MWM than rats fed the chow diet alone or chow and supplemental fat. Additionally, when tested 10 days after the initial training trials, rats given sucrose displayed deficits in long-term spatial memory. After 6 weeks on the diets, fasting blood glucose and serum triglyceride concentrations were significantly higher in sucrose-fed rats than in rats eating only the standard diet. These results indicate that diet-induced obesity resulting from excess sucrose intake, but not fat intake, in young animals impairs spatial learning and memory. It is hypothesized that these deficits arise from metabolic insults that leave the brain vulnerable to alterations in insulin sensitivity and glucose metabolism.     

Effects of early protein malnutrition and scopolamine on learning and memory in the Morris water maze

The present study investigated the effects of early protein malnutrition on the spatial learning and memory processes. The consequences of malnutrition for the cholinergic system were evaluated by comparing the performance of malnourished and control animals in the Morris water maze after treatment with scopolamine. The learning test consisted of placing the animal in the maze to escape to a submerged platform with 12 trials per day for two consecutive days. After 24 trials, the platform was removed, the rats were placed in the maze and the time spent by them in each quadrant was recorded. After 28 days the animals were tested in a single trial to verify the retention of the spatial information. In the first Experiment, scopolamine (0.0, 0.2, 0.4 and 0.6 mg/kg per ml. i.p.) was administered 20 min before the experimental sessions. In the second experiment, a dose of 0.6 mg/kg was administered after the sessions, during the period in which learning consolidation occurs. In the first experiment, there was a significant effect of the drug, with scopolamine impairing, learning in both nutritional conditions. In the saline condition, control animals presented a better performance when compared with malnourished animals. However, 28 days later, both groups increased their latencies. With 0.2 and 0.4 mg/kg of scopolamine, the performance of both nutritional groups was similar and with 0.6 mg/kg malnourished animals performed better than controls. In the second experiment, malnourished animals were also less reactive to the effects of scopolamine, resulting in lower impairments as compared to control animals. These data suggest long-term changes in learning and memory as the result of changes produced by protein malnutrition in the cholinergic neurotransmitter system.