APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder

Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society. Valid animal models for this uniquely human condition should exhibit histopathological, biochemical, cognitive, and behavioral alterations observed in Alzheimer's disease patients. Major progress has been made since the understanding of the genetic basis of Alzheimer's disease and the development and improvement of transgenic mouse models. All present Alzheimer's disease models developed are partial but nevertheless essential in further unraveling the nature and spatial and temporal development of the complex molecular pathology underlying this condition. One of the more recent transgenic attempts to model Alzheimer's disease is the APP23 transgenic mouse. This article describes the development and assessment of this human amyloid precursor protein overexpression model. We summarize histopathological and biochemical, cognitive and behavioral observations made in heterozygous APP23 mice, thereby emphasizing the model's contribution to clarification of neurodegenerative disease mechanisms. In addition, the first therapeutic interventions in the APP23 model are included.     

Tool-use learning in Tonkean macaques (Macaca tonkeana)

The transmission of tool use is a rare event in monkeys. Such an event arose in a group of semi-free-ranging Tonkean macaques (Macaca tonkeana) in which leaning a pole against the parks fence (branch leaning) appeared and spread to several males. This prompted us to test individual and social learning of this behavior in seven young males. In the first experiment, three males learned individually to obtain a food reward using a wooden pole as a climbing tool. They began using the pole to retrieve the reward only when they could alternatively experience acting on the object and reaching the target. In a second experiment, we first tested whether four other subjects could learn branch leaning after having observed a group-mate performing the task. Despite repeated opportunities to observe the demonstrator, they did not learn to use the pole as a tool. Hence we exposed the latter subjects to individual learning trials and they succeeded in the task. Tool use was not transmitted in the experimental situation, which contrasts with observations in the park. We can conclude that the subjects were not able to recognize the target as such. It is possible that they recognized it and learned the task individually when we alternated the opportunity to act upon the object and to reach the reward. This suggests that these macaques could then have associated the action they exercised upon the pole and the use of the pole as a means to reach the reward.     

Mood-congruent attentional bias in dysphoria: maintained attention to and impaired disengagement from negative information

Attentional bias to negative information has been proposed to be a cognitive vulnerability factor for the development of depression. In 2 experiments, the authors examined mood-congruent attentional bias in dysphoria. In both experiments, dysphoric and nondysphoric participants performed an attentional task with negative, positive, and neutral word cues preceding a target. Targets appeared either at the same or at the opposite location of the cue. Overall, results indicate that dysphoric participants show maintained attention for negative words at longer stimulus presentations, which is probably caused by impaired attentional disengagement from negative words. Furthermore, nondysphoric participants maintain their attention more strongly to positive words. These results are discussed in relation to recent developments in the pathogenesis and treatment of depression.     

The odd-even effect in addition: an analysis per problem type

The odd-even effect is a well documented finding in the literature on mental arithmetic, at least for multiplication. It implies that false answers with the same parity as the correct answer are rejected more slowly than false answers with a different parity. For addition, this effect is not so well documented. The study by Krueger and Hallford (1984) is the only one that investigated odd-even effects for addition. However, they did not investigate odd-even effects per problem, even though there are indications that problem type can modulate odd-even effects for multiplication (Lemaire & Reder, 1999). Therefore, we wanted to get more insight into odd-even effects for addition by investigating odd-even effects per problem type. Our results extended the findings of Krueger and Hallford. First of all, we found an interaction between split and problem type. The most important and new result of present study, however, was a strong parity effect for E + E problems. We discuss our results in terms of two alternative explanations for odd-even effects, namely use of a parity rule on the one hand and familiarity with even outcomes on the other.     

Automatic processing of dominance and submissiveness

We investigated whether people are able to detect in a relatively automatic manner the dominant or submissive status of persons engaged in social interactions. We used a nonaffective variant of the affective Simon paradigm of De Houwer and Eelen (1998) in which participants responded by saying either "dominant" or "submissive" depending on the right or left spatial position of a target person who was engaged as either the dominant or the submissive agent in a social interaction. We observed that responses were facilitated when the status connotation of the target person and the correct response corresponded. These results provide new information about the automatic nature of information related to emotion-antecedent appraisals.     

Decline in working memory updating through ageing: intrusion error analyses

The present research examines the decline in working memory updating through age. Two experiments compared groups of participants in different age ranges (young-old, 55-65 years, old, 66-75 years and old-old, more than 75 years and, in Experiment 2 only, young, 20-30 years). Memory updating tasks were administered, which required participants to remember the smallest items in each list. To perform the task correctly, participants had to update information efficiently, reducing interference from items no longer relevant. Intrusion errors were computed and in the first experiment these were described as "intrusions of irrelevant items" (immediate exclusion) and "intrusions of once relevant items" (delayed exclusion). The oldest adults performed worse in memory updating and made a greater number of intrusion errors of once relevant information. In the second experiment results showed that increases in memory load (number of items that had to be remembered) and updating demand (number of potentially relevant items) impaired performance. The oldest adults had greater difficulty when the task demand was increased. Furthermore, they produced a higher number of intrusion errors, particularly when the updating demand was increased. It therefore appears that elderly people have specific difficulty in updating information in working memory by excluding irrelevant information.     

The old and thee, uh, new: disfluency and reference resolution

Most research on the rapid mental processes of on-line language processing has been limited to the study of idealized, fluent utterances. Yet speakers are often disfluent, for example, saying "thee, uh, candle" instead of "the candle." By monitoring listeners' eye movements to objects in a display, we demonstrated that the fluency of an article ("thee uh" vs. "the") affects how listeners interpret the following noun. With a fluent article, listeners were biased toward an object that had been mentioned previously, but with a disfluent article, they were biased toward an object that had not been mentioned. These biases were apparent as early as lexical information became available, showing that disfluency affects the basic processes of decoding linguistic input.     

The closer we are,the more we are alike: The effect of self-other merging on depersonalized self-perception

The present study examined whether or not the extent to which people include other group members in the self, influences depersonalized self-perception (i.e., perceiving self and others as similar in terms of group characteristics). The results revealed that self-other merging positively influenced feelings of belongingness and identification with the in-group. Furthermore, a strong experience of self-other merging was shown to lead to depersonalized self-perception as measured by a self-assimilation and an in-group homogeneity index. Finally, results also revealed that feelings of belongingness and group identification mediated, at least partly, the effect of self-other merging on depersonalized self-perception. The findings are discussed in light of the literature on self-expansion.     

Extinction-induced immobility in the water maze and its neurochemical concomitants in aged and adult rats: a possible model for depression?

Extinction of escape behavior in the water maze due to the removal of the platform, was hypothesized to induce a negative state, including the development of immobility, which is held to reflect a state of "despair" when measured in the forced swimming test. 27 aged and 8 adult animals (26 and 3 months old Wistar rats, respectively) were tested in the water maze during nine days with a platform hidden, followed by 7 days of extinction trials with the platform absent. As expected, both age groups developed immobility over the extinction trials, with the aged showing more than the adults. To examine whether the age difference in immobility was related to performance differences during acquisition, the aged were subdivided into superior, intermediate and inferior learners (n = 9 per group) on the basis of overall times to platform during acquisition, and compared with each other and the adults. Results showed that the aged inferior learners displayed the highest levels of immobility among the aged. Immobility scores were then correlated with post-mortem neurotransmitter contents in the hippocampus and ventral striatum. In the ventral striatum, levels of immobility were correlated with levels of acetylcholine, dopamine and the metabolite dihydroxyphenylacetic acid in the aged, and with norepinephrine in the adults. The data support the hypothesis that multiple extinction trials in the water maze result in immobility that may indicate "behavioral despair," and that striatal neurotransmitter systems correlate with the degree of its expression. The concept of extinction-induced despair is held to provide the promise of a conceptual and empirical model of human depression that is the consequence of loss of reinforcers.