Effects of arachidonic acid on the spatial cognition of aged rats

Abstract:  To examine the effects of arachidonic acid (AA) on age-related cognitive deficits, Fischer 344 rats were given an AA-supplemented powder diet for 12 weeks from 18.6 months old as part of the old AA (OA) group. Other age-matched rats were fed a non-AA-supplemented powder diet as part of the old control (OC) group, and young rats were fed lab pellets as part of the young control (YC) group. When the aged rats reached 20.0 months old, all animals were tested for spontaneous activity in an open field, followed by the Morris water maze place and cue tasks. Escape latencies for the place task showed that the YC rats were fastest, and there was no difference between the OA and OC groups. However, the probe test and the first block of the cue task indicated that the OA rats remembered the location of an invisible platform better than the OC rats. Although the amount of hippocampal AA was larger in the OA rats than in the OC rats, the difference was not significant. The results showed that AA administration to aged animals may alleviate age-related deficits in spatial cognition.     

Sex differences and estropausal phase effects on water maze performance in aged rats

An age-related decline in memory has been reported in male rats; however, there are few studies that have addressed these changes in aged female rats. In young female rats, hormonal cycles influence behavior. By the age of 22 months most female rats have not had regular hormonal cycles for at least 9 months. In the current study we examined how the hormonal status (persistent estrus and pseudo-pregnant) of the aged (22-24 months) female rat (Long Evans) influenced performance on a spatial version of the Morris water maze and compared this to aged male rats. Aged females in persistent estrus showed better performance on the water maze than both aged females that were pseudopregnant and aged males. Thus, postestropausal hormonal status may influence the course of aging in females.     

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.     

Age differences in sleep-wake behavior under natural conditions.

Differences in lifestyle may account for a considerable portion of the reported age-related changes in overt circadian rhythmicity. By instructing a group of healthy, noninstitutionalized, elderly subjects and a group of young adults to keep a sleep-wake log for a period of two weeks, and to wear an activity monitor for an overlapping period of 11 days, we attempted to assess age-related differences in the habitual sleep-wake behavior, in particular its day-to-day variability. Four clusters of coherent variables were constructed, reflecting (1) circadian phase, (2) variability of sleep-wake behavior, (3) sleep-wake continuity and (4) subjective sleep-wake quality. The results showed that, in comparison with the young subjects, the elderly had a relatively advanced and more regular sleep-wake pattern, reported more midnight awakening and did not differ in their subjective sleep evaluation. In spite of a greater regularity in their lifestyle (which would favor a larger amplitude of the overt circadian rhythmicity) oral temperature measurements showed some evidence of a weakened 24-h periodicity in the elderly.     

Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats

Normal aging is associated with disruption of neural systems that subserve different aspects of cognitive function, particularly in the hippocampus and frontal cortex. Abnormalities in hippocampal function have been well investigated in rodent models of aging, but studies of frontal cortex function in aged rodents are few. We tested young (4–5 mo old) and aged (27–28 mo old) male Long-Evans rats on an attentional set-shifting task modified slightly from previous publication. After training on two problems in which the reward was consistently associated with the same stimulus dimension, and a reversal of one problem, a new problem was presented in which the reward was consistently associated with the previously irrelevant stimulus dimension (extradimensional shift [EDS]). Aged rats as a group were significantly impaired on the EDS, although some individual aged rats performed as well as young rats on this phase. In addition, some aged rats were impaired on the reversal, although a group effect did not reach significance in this phase. Impairment in neither reversal nor EDS was associated with impairments in spatial learning in the Morris water maze. Young rats with neurotoxic lesions of medial frontal cortex are also selectively impaired on the EDS. These results indicate that normal aging in rats is associated with impaired medial frontal cortex function. Furthermore, age-related declines in frontal cortex function are independent of those in hippocampal function. These results provide a possible basis for correlating age-related changes in neurobiological markers in frontal cortex with cognitive decline.     

Effects of opiate antagonists on spatial memory in young and aged rats

The effects of post-training opiate antagonist administration on spatial memory were assessed in young and aged male Long Evans rats. In Experiment I rats were trained to visit each arm of an eight-arm radial maze once in a session to obtain a food reward placed at the end of each arm. During training aged rats required significantly more trials to achieve criterion performance when compared to young mature rats. However, administration of the opiate antagonist naloxone (2.0 mg/kg) immediately after each training trial did not significantly alter the rate of achieving accurate performance in either age group. In Experiment II young and aged rats that were previously trained to a comparable criterion on the radial maze were tested on the same maze apparatus in novel spatial environments. When animals were exposed to novel spatial information, the effects of post-trial opiate antagonists were examined using a within-subjects counter-balanced design. In Experiment IIa naloxone (2 mg/kg) enhanced the performance of both young and aged rats. In Experiment IIB naltrexone (1.0 mg/kg) was found to have a comparable effect of enhancing the performance of both age groups. In addition, in Experiment IIb a significant age-related deficit was found in rats tested in novel spatial environments. These results indicate that opiate antagonists are capable of improving memory for new spatial information in both young and aged rats on a task that is sensitive to behavioral deficits during normal aging.     

Regulation of Peripheral Catecholamine Responses to Acute Stress in Young Adult and Aged F-344 Rats

Young adult (3-month-old) and aged (24-month-old) Fischer-344 male rats received i.v. infusions of 3H-labeled norepinephrine (NE) and epinephrine (EPI) to examine the effects of aging on the neuronal uptake of NE and sympathoadrenal release of NE and EPI. Spillovers of NE and EPI into plasma and their clearance from the circulation were estimated from plasma concentrations of endogenous and 3H-labeled NE and EPI. The efficiency of neuronal uptake was assessed from changes in plasma clearance of NE and concentrations of its intraneuronal metabolite, dihydroxyphenylglycol (DHPG), during immobilization stress or neuronal uptake blockade with desipramine. Stress-induced increases in plasma NE and higher plasma NE concentrations in aged compared to young adult rats were due to both decreases in NE clearance and increases in NE spillover. EPI spillover and clearance were reduced in aged compared to young adult rats, so that plasma EPI levels did not differ between groups. Young adult and aged rats had similar desipramine-induced decreases in NE clearance, whereas desipramine-sensitive decreases and stress-induced increases in plasma DHPG were larger in aged rats. This indicates that neuronal uptake is intact and that increased NE spillover at rest and during stress in aged rats reflects increased NE release from sympathetic nerves. The results show that aging is associated with divergent decreases in EPI release from the adrenal medulla and increases in NE release from sympathetic nerves. Increased plasma concentrations of NE in aged compared to young adult rats also result from decreased circulatory clearance of NE, but this does not reflect any age-related impairment of NE reuptake.     

The effects of guanfacine, alpha-2 agonist, on the performance of young and aged rats in spatial navigation task.

The aim of the present experiment was to study the effects of a low dose (0.001 mg/kg) of guanfacine, alpha-2 agonist, on the acquisition and retention of a water maze task measuring spatial reference memory in young and aged rats. Aged rats were impaired in the acquisition of this task. Both young and aged rats treated with guanfacine had shorter escape latencies than their saline treated counterparts. However, guanfacine treatment increased the speed of swimming in aged rats. According to the results of the probe trial, guanfacine may slightly improve the acquisition/retention of water maze task in young rats, whereas it may slightly impair the acquisition/retention of aged rats. The results suggest that a low dose of guanfacine administered peripherally may have different effects on young and aged rats in water maze performance, and a low dose of guanfacine does not improve spatial reference memory in aged rats.     

Age-Related Changes in Plasma Catecholamine Responses to Acute Swim Stress

Young adult (3 months) and aged (22 months) Fischer 344 male rats were prepared with chronic tail artery catheters. Three days after surgery, rats were exposed acutely to swim stress at 20, 25, 30, or 35°C for 15 min. Blood samples were obtained from each rat under basal conditions, at the end of the swim stress episode, and 15, 30, and 45 min after swim stress. Basal plasma levels of norepinephrine and epinephrine (EPI) were similar for 3- and 22-month-old rats. In contrast, plasma catecholamine responses of aged rats were significantly greater than those of young adult rats following swim stress at 20 and 25°C. Plasma catecholamine responses were similar for rats of the two ages following swim stress at 30 or 35°C. These findings indicate that aged rats have exaggerated sympathetic-adrenal medullary responses to acute swim stress at the lower water temperatures. Given the modulatory effects of plasma EPI on memory, these age-related alterations in plasma catecholamine responses to acute swim stress may influence spatial memory performance of rats in the Morris water maze.     

Effects of green tea extract on learning, memory, behavior and acetylcholinesterase activity in young and old male rats

Objective

To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats.

Methods

Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity.

Results

Treatment of young and old rats with the extract resulted in no significant difference in performance on the rota rod treadmill test/righting reflex time. Green tea extract significantly improved learning and memory in older rats, with increased retention latency to enter difference in passive avoidance test. In the elevated maze test, green tea treatment resulted in significantly more number of entries in the enclosed arm by the young and old rats. Decline in acetylcholinesterase activity was observed in the cerebrum of green tea treated old rats in comparison to the green tea treated young rats.

Conclusion

Green tea extract administration is effective in enhancing learning and memory in aged rats, and hence, may serve useful in reversing age-related deficits.     

Increased novelty-induced grooming in aged rats: a preliminary observation

Age-related changes in grooming activity in female Fischer-344 rats were observed in a home cage and in a novel testing chamber for 50 min. Compared to the home cage condition with brief handling treatment, excessive grooming was found in the novel situation. The amount of novelty-induced grooming of aged rats (26-28 months) was about two times that of young animals (6-8 months). This increase in novelty-induced grooming of aged animals was attributable to an increase in the number of grooming bouts, prolongation of each grooming bout, and a slight increase in the duration of licking elements. However, there were no age differences in the percentage of face washing and the duration of face-washing elements. These results are discussed in terms of behavioral aging and age-related changes in peptidergic pathways in the brain.     

Short forms of the "reference-" and "working-memory" Morris water maze for assessing age-related deficits.

Short forms of the reference- and working-memory versions of the Morris water maze, each limited to 10 trials, were examined for their reliability and sensitivity to age-related deficits in 16- and 24-month F-344 rats, relative to 2- to 2.5-month young controls. The reference-memory task used long intertrial intervals of 23 h, but required learning only one target location, while the working-memory task used shorter intertrial intervals of 60 min but required learning many different target locations. The reference-memory task was very reliable, revealed large age-related deficits, and correctly identified almost all aged rats as impaired relative to young controls. The working-memory task was less reliable, revealed smaller deficits than the reference memory task at 24 months, and did not discriminate as well between 2.5- and 24-month rats. Furthermore, in the working-memory task 16- and 24-month rats had longer swim paths than 2- to 2.5-month rats on the first trial of each trial pair, which is suggestive of a deficit in processing spatial information and raises questions about the validity of this test as a specific test of working memory. Although the working-memory procedures may be preferable under certain conditions, perhaps as a measure specific to hippocampal dysfunction, the reference-memory task seems more sensitive to age-related deficits and more accurately identifies older rats as impaired. These results are consistent with previous reports that age-related deficits in acquiring spatial learning tasks are common and that the magnitude of the deficit increases as the length of the retention interval increases.     

Rapid forgetting of social transmission of food preferences in aged rats: relationship to hippocampal CREB activation

A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB- and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.     

Glucose attenuation of paradoxical sleep deficits in old rats.

Glucose administration enhances memory in several amnestic populations, including old humans and rodents. The present experiment demonstrates that glucose also enhances measures of sleep in old rats. Three-hour day-time sleep EEGs were assessed in 3- and 24-month-old rats. The animals received injections of saline or glucose (100, 500, and 1000 mg/kg) on different days in a counter-balanced order. At doses of 100 and 500 mg/kg, glucose augmented the duration of paradoxical sleep bouts and total paradoxical sleep time in old, but not young, rats. Within 2 weeks after the sleep tests, measures of several brain neurotransmitter functions were obtained. Glucose was more effective in enhancing paradoxical sleep in those individual aged rats with high levels of hippocampal choline acetyltransferase and occipital cortex serotonin concentrations than in aged rats with lower levels on these neurochemical measures. The findings suggest that glucose attenuates selective age-related sleep deficits in old rats. More generally, these results add to a growing body of evidence indicating that moderate doses of peripheral glucose can influence a variety of CNS measures.     

Long-term memory loss in senescent rats: neuropsychological analysis of interference and context effects

Four experiments are reported in which normal, senescent (25-27 months) and young adult (6 months) rats were tested for recall of a passive avoidance response 1 hr or several weeks after conditioning. There were no age differences at the 1-hr test, but a decrement was observed in old rats tested under standard conditions after long delays. The age-related impairment was exaggerated when additional approach training was administered in an identical apparatus between avoidance conditioning and testing. When the approach training was administered in an apparatus that contrasted markedly from the original, no age differences were observed. It was concluded that increased susceptibility to interference and contextual factors contributed to rapid forgetting in old rats, a pattern very similar to that observed previously in young adult rats with selective lesions to the hippocampus.     

Individual Differences in Spatial Memory and Striatal ChAT Activity among Young and Aged Rats

Individual differences in spatial memory among young and aged rats were assessed using memory tasks related to integrity of the hippocampus and the neostriatum. Relationships were then examined between measures of spatial memory and regional choline acetyltransferase (ChAT) activity, a marker for cholinergic integrity. Twenty-four-month-old Long-Evans rats were impaired in comparisons with 6-month-old rats on measures of place learning, working memory, reference memory, and perseveration in water-maze tasks. Aged rats that were impaired on one measure of memory, however, were not necessarily impaired on other measures. ChAT activity in the ventromedial and dorsolateral neostriatum of aged rats was significantly reduced in comparisons with young rats whereas no difference was found in the hippocampus. Aged rats with the most ChAT activity in the anterior ventromedial neostriatum performed best on the place-learning and reference memory tasks but also made the most perseverative errors on the working memory task. In addition, young and aged rats with the most ChAT activity in the anterior dorsolateral neostriatum were those with the least accurate working memory. No relationships were found between ChAT activity in the hippocampus and spatial memory. Thus age-related memory impairment has components that can be segregated by measuring relationships between cholinergic integrity in subregions of the anterior neostriatum and memory tasks with different strategic requirements.     

Choline Uptake in the Frontal Cortex Is Proportional to the Absolute Error of a Temporal Memory Translation Constant in Mature and Aged Rats

The relationship between the magnitude of the error in the content of temporal memory and sodium-dependent high-affinity choline uptake (SDHACU) in the frontal cortex and hippocampus was examined in mature (10- to 16-month-old) and aged (24- to 30-month-old) male rats. The peak time of the response rate distribution that relates the probability of a response to signal duration in a 20-s peak-interval timing procedure was used to index the remembered time of reinforcement. Regression analyses indicated that SDHACU in the frontal cortex of both mature and aged rats and in the hippocampus of aged rats is proportional to the absolute error in the content of temporal memory. These biochemical effects of peak-interval training were also compared with biochemical measures taken from control rats that received random-interval training. This comparison indicated that the observed changes in SDHACU were dependent upon the predictability of the programmed time of reinforcement and age-related changes in memory encoding and retrieval.     

Light-dark variation and changes across the lactational period in the behaviors of undisturbed mother and infant guinea pigs (Cavia porcellus)

Lactating guinea pigs (Cavia porcellus) and their litters were observed by videophotography across the light/dark cycle at 1, 11, 21, and 31 days postpartum. The highest level of behavioral activity was seen in the dark, particularly in the hour after light offset. This circadian pattern was evident from Day 1 in mothers and from Day 11 in pups. Contact between mothers and pups was inversely related to activity, occurring more frequently during light. Maternal grooming of pups occurred on Day 1 and then declined: self-grooming by pups increased across days. Intake of solid food and water by pups occurred on Day 1 and increased thereafter. A nearly complete transition from nursing to independent ingestion was observed between 21-31 days of age. Overall, we document several ontogenetic changes in young guinea pigs and demonstrate that under laboratory conditions mother and infant guinea pigs exhibit a nocturnal activity pattern.