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Characteristics of learning and memory in streptozocin-induced diabetic mice.

We demonstrated that mice with streptozocin-induced diabetes mellitus have normal acquisition for relatively simple tasks but show problems in learning more complex tasks such as shuttle box avoidance. Enhanced learning previously reported in simple passive avoidance tasks appears to be due to increased foot shock sensitivity. Diabetic mice show a marked memory retention deficit after learning an active avoidance T-maze task. This retention deficit was reversed by a single injection of insulin, suggesting that it may be related to hyperglycemia per se. Diabetic mice have a shift to the left in the inverted U-shaped dose-response curve for memory retention produced by the acetylcholine agonist arecoline. Based on a preliminary screening, responses to several other pharmacological memory enhancers are probably altered in diabetic mice. These studies suggest that this mouse model of diabetes mellitus demonstrates a deficit in memory retention and retrieval similar to that seen in humans with diabetes mellitus.

Animals↗

Evidence for interactions between central noradrenergic neurons and adrenal hormones in learning and memory.

The role of ascending noradrenergic projections in the acquisition and retention of a passive avoidance step-down response was evaluated by means of bilateral stereotaxic 6-hydroxydopamine-induced lesions of these systems. Lesions of the dorsal NA bundle alone, or in combination with lesions of the ventral NA bundle, failed to influence either the acquisition or retention of the passive avoidance response. In contrast, animals subjected to dorsal and ventral NA bundle lesions and adrenalectomy exhibited severe deficits in both the acquisition and retention of this response, and this effect was of the same magnitude as was observed after posttrial injections of diethyldithiocarbamate (DDC, 300 mg/kg). Adrenalectomy by itself had a small but significant effect on retention but did not influence acquisition of the response. The results are discussed with reference to the possibility that interactions between adrenal hormones and central NA mechanisms may serve important roles in learning and memory. However, the data provide no support for the hypothesis that central NA neurons are, by themselves, critically involved in these phenomena.

Adrenalectomy↗

Working memory and learning in early Alzheimer's disease.

Cognitive deficits associated with early Alzheimer's disease (AD) have been recently operationalised in terms of an acquisition deficit and the research supporting this view is presented. However, there is still debate concerning the nature of this deficit and how underlying cognitive processes may be detrimentally affecting the ability to acquire new information in early AD. This review argues that the pattern of cognitive deficits contributing to the acquisition impairment in early AD patients may be readily interpreted within the context of a working memory model. Isolating the component processes of working memory that underlie the acquisition deficit in early AD patients will aid in the design of clinical applications that are focussed at enhancing the ability to acquire new information in everyday life.

Alzheimer Disease↗

Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats.

Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 +/- 10%) and significantly prolonged acquisition (398 +/- 62 s) and shortened retention (79 +/- 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 +/- 8%), they performed significantly better in the passive avoidance task (255 +/- 36 s and 145 +/- 18 s in acquisition and retention) than the vehicle-treated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSF-treated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task.

Acetylcholinesterase↗

Impairment of learning and memory in rats caused by oxidative stress and aging, and changes in antioxidative defense systems.

To elucidate the influence of oxidative stress on the brain functions during aging, the cognitive performance ability of rats was assessed by using the water-maze test as an oxidative stress before and after hyperoxia. Young rats showed significantly greater learning ability than both old rats and vitamin-E-deficient rats. Although the memory functions of all rats were Impaired after oxidative stress, the memory retention of young rats was greater than those of other groups. After the stress, none of the rats recovered their learning ability. During aging and through hyperoxia, the release of acetylcholine from nerve terminals was remarkably decreased. Instead, thiobarbituric acid reactive substance (TBARS) contents in rat hippocampus and cebral cortex, and their synaptic membranes, were significantly increased during aging and by oxidative stress. The antioxidative defense system in rat brain was also changed by the stress. These results suggest that oxidative stress may contribute to learning and memory deficits following oxidative brain damage during aging.

Acetylcholine↗

Cholinergic septal grafts into the hippocampal formation improve spatial learning and memory in aged rats by an atropine-sensitive mechanism.

Behaviorally impaired old rats were selected from a population of 75 21- to 23-month-old rats on the basis of the place-investigated abilities in the Morris' water-maze task. After the pretransplant test, half of the old impaired rats received bilateral intrahippocampal cell suspension grafts prepared from the fetal septal-diagonal band region, which is rich in developing cholinergic neurons; the other half were left as sham-operated controls. Twelve weeks after grafting, the rats were retested in the water-maze using alternating cue-navigation and place-navigation trials (i.e., with visible or nonvisible escape platform). While the old impaired controls had deteriorated further between the 2 tests and showed poor retention of the pretransplant performance level, the grafted rats were significantly improved in comparison with both their pretransplant performance and the performance of the old impaired controls in the posttransplant test. The graft-induced effect was due both to an improved retention of the performance level acquired in the test performed prior to transplantation surgery, and to an improved acquisition of spatial memory of the escape platform site during the posttransplant test week (measured as an improved focusing of search over the platform site after platform removal). The acetylcholine esterase inhibitor physostigmine had no or only marginal effects on the performance of any of the young or aged rat groups. By contrast, the recovered navigational abilities and spatial memory in the grafted animals were completely abolished after administration of the muscarinic receptor antagonist atropine. A similar atropine-sensitivity was seen in behaviorally nonimpaired aged rats but not in the well-trained young control rats. The results show that cholinergic septal grafts, implanted into the hippocampal formation, improved spatial learning in the impaired aged rats primarily, or perhaps exclusively, by a recovery of the rats' ability to use spatial cues for place-navigation in the water-maze, while other aspects of the performance deficits in the water-maze task in the aged rats were left unaffected by the septal grafts. On the basis of parallel morphological studies, it is proposed that the effects of the septal grafts on the spatial learning impairments in the aged rats are critically dependent on the direct action of cholinergic neurons in the grafts via synapses formed onto neuronal elements in the host by their ingrowing axons.

Aging↗

Inhibition of nitric oxide (NO) production selectively impairs learning and memory in the rat.

Animals administered the nitric oxide (NO) synthase inhibitor N-w-nitro-L-arginine methyl ester (NAME) for five days exhibited severe deficits in acquisition of a place-navigation learning task. The effect of NAME was selective to place-navigation learning. NAME had no effect on sensorimotor or motivational processes in a related task. These results are consistent with the view that NO participates in learning and execution of memory tasks.

Animals↗

Learning and memory: recent findings.

Recent findings from neuroimaging, event-related potential and lesion investigations reflect a rapidly emerging view that the memory system is widely distributed throughout the cortex. It is clear that the pattern of cortical involvement during encoding and retrieval of memories is critically dependent on the nature and complexity of task demands. This has implications, both for existing models of memory function, and in the methodology of future investigations and the issues they address. No consensus has yet been reached on a number of issues, perhaps most notably the role of the hippocampus in retrieval, but advances in measurement techniques should enable some of these matters to be resolved. Further work must address the complex dynamics of the memory system, the extent to which the same regions underlie different functions, and how different regions interact and reflect common functions.

Animals↗

Acute stress in pregnant rats: effects on growth rate, learning, and memory capabilities of the offspring.

Growth rate of the offspring of female rats stressed by the presence of a cat at the 10th or the 19th gestational day was lower than that of controls whereas footshocks administered at the same periods did not significantly influence growth rate of the young. Whatever the nature of the stress and the time when it was administered to the mother, the death rate of the young rats was much greater than that in controls. When adult, the offspring of stressed mothers exhibited learning and memory impairments in a delayed alternation task as well as in passive avoidance conditioning. Alteration of these cognitive functions is interpreted in terms of subtle dysfunctions in the development of the nervous system through modifications of the hormonal components of the mothers, particularly eventual alterations of the nervous system biochemistry of the offspring.

Animals↗

[Learning and memory in antenatal alcohol exposure].

The ability to the training in a T-shape maze was studied in the progeny of rats given 20% alcohol in a dose of 2 g/kg during pregnancy. The studies were performed according to the method of successive alternation of the left and right runs with food reinforcement. One-month-old rats were less capable of training and had a worse long-term memory as compared to controls. The differences in the training of the experimental and control animals had diminished by the age of 2 months.

Animals↗

Effects of systemic administration of beta-casomorphin-5 on learning and memory in mice.

The effects of systemic administration of bovine beta-casomorphin-5 (Tyr-Pro-Phe-Pro-Gly), a mu-opioid receptor agonist derived from milk beta-casein, on spontaneous alternation behavior in the Y-maze (spatial short-term memory) and step-down-type passive avoidance response (non-spatial long-term memory) were investigated in mice. Intraperitoneal (i.p.) administration of beta-casomorphin-5 (0.1-20 mg/kg) did not have a significant effect on either spontaneous alternation behavior or passive avoidance response. However, a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improved scopolamine (1 mg/kg, s.c.)-induced impairment of spontaneous alternation behavior and passive avoidance response. Pretreatment with intracerebroventricular injections of beta-funaltrexamine (a mu-opioid receptor antagonist, 0.1 microg/mouse) and naloxonazine (a mu(1)-opioid antagonist, 5 microg/mouse), which did not improve scopolamine-induced impairment, prevented the ameliorating effect of beta-casomorphin-5 on scopolamine-induced impairment of passive avoidance response. These results indicated that systemic administration of a low dose (1 mg/kg, i.p.) of beta-casomorphin-5 improves the disturbance of learning and memory resulting from cholinergic dysfunction through central mediation involving mu(1)-opioid receptors.

Analgesics↗

Evaluation of learning and memory dysfunction and histological findings in rats with chronic stage contusion and diffuse axonal injury.

We previously reported a modified fluid percussion device capable of consistently producing experimental cortical contusion (CC) and diffuse axonal injury (DAI) in separate groups of rats by lateral and midline fluid percussion, respectively. The purpose of the present study was to compare the differences in learning acquisition and memory retention impairments between these two types of injured rats in the chronic stage using the Morris water maze technique. We also compared the histological differences between these two different types of traumatic brain injury. The results showed a statistically significant difference in learning acquisition impairment between the sham and CC rats and also between the sham and DAI rats. However, a significant difference in memory retention impairment was observed only between the sham and DAI rats. Histologically, the neuronal cell loss of CA3 pyramidal cells in the hippocampus was observed on the ipsilateral side in the CC and bilaterally in DAI. The neuronal cell loss was seen in bilateral entorhinal cortex layer II in DAI, but it was not seen in CC. From these results, we speculate that the marked cell loss in the hippocampus CA3 region in both CC and DAI rats was related to the impairment of spatial learning acquisition. The marked cell loss in entorhinal cortex layer II in DAI rats may be one of the important factors in the impairment of spatial memory retention.

Animals↗